Pomalidomide and Dexamethasone With or Without Ixazomib in Treating Patients With Relapsed Multiple Myeloma

Multiple Myeloma in Relapse Clinical Trial

Official title:

A Phase I/II Study of Pomalidomide, Dexamethasone and Ixazomib vs. Pomalidomide and Dexamethasone for Patients With Multiple Myeloma Relapsing on Lenalidomide as Part of First Line Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02004275
• Other study ID #: A061202
• Secondary ID: NCI-2013-01702U1
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 2014

Study information

• Verified date: November 2023
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase I/II trial studies the side effects and best dose of pomalidomide and ixazomib when given together with dexamethasone and to see how well pomalidomide and dexamethasone with or without ixazomib works in treating patients with multiple myeloma that has come back. Biological therapies, such as pomalidomide and dexamethasone, may stimulate the immune system in different ways and stop cancer cells from growing. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pomalidomide and dexamethasone are more effective with or without ixazomib in treating multiple myeloma.

Description:

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) for combination therapy pomalidomide/dexamethasone/ixazomib. (Phase I) II. To assess whether the combination of pomalidomide/dexamethasone/ixazomib improves progression-free survival (PFS) relative to pomalidomide/dexamethasone. (Phase II)

SECONDARY OBJECTIVES:

I. To determine dose-limiting toxicities (DLTs). (Phase I) II. To analyze type and grade of all serious adverse events (SAEs). (Phase I) III. To analyze type and grade of all adverse events (AEs). (Phase I) IV. To analyze the reason for and incidence of dose modifications/omissions/delays. (Phase I) V. To assess preliminary evidence of clinical efficacy. (Phase I) VI. To assess whether the overall response rate (ORR), partial response (PR), very good partial response (VGPR), complete response (CR) or stringent CR (sCR) rate differ with respect to treatment regimen. (Phase II) VII. To assess the clinical benefit rate (CBR: minimal response [MR] + ORR) for pomalidomide/dexamethasone/ixazomib compared to pomalidomide/dexamethasone. (Phase II) VIII. To assess the disease control rate (DCR: stable disease [SD] + CBR) for pomalidomide/dexamethasone/ixazomib compared to pomalidomide/dexamethasone. (Phase II) IX. For those patients achieving a PR or better, we will assess whether the combination of pomalidomide/dexamethasone/ixazomib increases the duration of response (DOR) compared to pomalidomide/dexamethasone. (Phase II) X. To assess whether the combination of pomalidomide/dexamethasone/ixazomib improves overall survival (OS) compared to those taking pomalidomide/dexamethasone alone. (Phase II) XI. To assess time to next treatment (TNT) for patients taking pomalidomide/dexamethasone/ixazomib compared to those on pomalidomide/dexamethasone. (Phase II) XII. To evaluate the safety of pomalidomide/dexamethasone/ixazomib compared with pomalidomide/dexamethasone. (Phase II) XIII. For patients on the pomalidomide/dexamethasone arm who opt to cross-over to the pomalidomide/dexamethasone/ixazomib arm, assessment of response rate (ORR, CBR, DCR), DOR, TNT, PFS and OS will be evaluated from date of cross-over. (Phase II) XIV. To determine if baseline level of perceived fatigue and overall quality of life (QOL) is associated with OS. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of pomalidomide and ixazomib followed by a phase II study.

After completion of study treatment, patients are followed up every 4 weeks until disease progression and then every 3 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 118
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• Histologically confirmed diagnosis of symptomatic multiple myeloma; relapsed disease is myeloma that has previously responded to prior therapy (MR or better) and subsequently progressed

• Patient must have measurable disease or non-measurable disease, defined as one or more of the following holding true:

• Measurable disease:

• Serum M-protein >= 1.0 g/dL (>= 0.5 g/dL for IgA or IgM myeloma) and/or

• Urine M-protein >= 200 mg/24 hours and/or

• Involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio

• For non-measurable disease:

• Baseline marrow burden of myeloma of at least 30%

• Progression on lenalidomide as part of first line therapy (lenalidomide-refractory disease)

• Lenalidomide-refractory disease is defined as disease progression on or progression within 60 days of the last dose of a lenalidomide-based treatment; patients should have received at least 2 cycles of a lenalidomide-based regimen to be evaluable for refractoriness; examples: 1) progression on lenalidomide maintenance therapy after initial induction +/- consolidation; 2) initial response followed by progression on continuous lenalidomide-dexamethasone +/- elotuzumab or daratumumab

• Pomalidomide naive disease

• Proteasome inhibitor naive or sensitive disease; proteasome inhibitor sensitive disease is defined as a PR or better to prior proteasome inhibitor-based therapy that is maintained for >= 60 days from the last dose of the proteasome inhibitor

• A patient who receives induction therapy with lenalidomide, bortezomib and dexamethasone and achieves a PR or better but subsequently progresses on continued lenalidomide or lenalidomide-dexamethasone would be eligible provided the progression occurs 60 days or more after discontinuation of the bortezomib; similarly, ixazomib exposure is allowed provided they meet the definition of proteasome inhibitor sensitive disease

• 1 prior line of systemic therapy for multiple myeloma, where a line of therapy for myeloma is defined as 1 or more planned cycles of single agent or combination therapy, as well as a planned series of treatment regimens administered in a sequential manner (e.g. lenalidomide, bortezomib and dexamethasone induction therapy for 4 cycles followed by autologous stem cell transplantation and then lenalidomide maintenance therapy would be considered 1 line of prior therapy); a new line of therapy begins when a planned therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, disease relapse or treatment-related toxicity (e.g. a patient is progressing in the face of lenalidomide maintenance therapy and has bortezomib and dexamethasone added into their regimen); a new line of therapy also begins when a planned treatment-free interval is interrupted by the need to start treatment due to disease relapse/progression (e.g. a patient with relapsed myeloma achieves a partial response after a planned 8 cycles of cyclophosphamide, bortezomib and dexamethasone, enjoys an 8-month period off therapy but then experiences disease progression requiring re-initiation of therapy)

• Allogeneic stem cell transplantation is allowed provided the patient is >= 1 year from transplant at time of registration, is not on immunosuppressive therapy to treat/prevent graft-versus-host disease, has no evidence of active graft versus host disease, and no evidence of active infection

• No other chemotherapy or radiation therapy within 14 days prior to registration

• No investigational therapy within 14 days prior to registration

• No major surgery within 28 days prior to registration

• No G-CSF (filgrastim) or GM-CSF (sargramostim) within 7 days of registration or pegfilgrastim within 14 days of registration to meet eligibility criteria

• No platelet transfusions within 7 days of registration to meet eligibility criteria; Note: red blood cell transfusions are allowed at any time

• A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Women of childbearing potential:

• Must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mlU/ml no more than 14 days prior to registration and must agree to repeat this test within 24 hours of starting pomalidomide

• Must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, before starting pomalidomide

• Must agree to ongoing pregnancy testing

• Must agree to not become pregnant or breast feed a child during treatment on this protocol

• Men must practice complete abstinence or agree to use a condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy

• Note: All participants must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

• Platelet count >= 50 x 10^9/L

• Calculated (Calc.) creatinine clearance >= 30 mL/min; calculated utilizing the Cockcroft-Gault formula or 24-hour urine collection

• Total bilirubin < 1.5 x upper limits of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limits of normal (ULN)

• Note: G-CSF and platelet transfusions cannot be used to increase counts to meet eligibility criteria

• Patients cannot have:

• Central nerve system involvement

• Primary refractory multiple myeloma, where primary refractory multiple myeloma is defined as disease that is nonresponsive - patients who have never achieved a minimal response (MR) or better - with any therapy over the course of their disease; it includes patients who never achieve MR or better in whom there is no significant change in M-protein and no evidence of clinical progression as well as patients who meet criteria for true progressive disease (PD)

• Primary or secondary plasma cell leukemia

• Light-chain (AL) amyloidosis or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

• Known active hepatitis C based on:

• +hepatitis C virus (HCV) antibody (confirmed)

• +HCV RNA

• Liver disease with history of positive serology

• Note: patients with a prior history of hepatitis C that has been successfully eradicated with antiviral therapy are eligible

• Known hepatitis B surface antigen positivity

• Previous hypersensitivity to any of the components of the study treatment

• Prior history of erythema multiforme with thalidomide or lenalidomide treatment

• =< grade 2 peripheral neuropathy

• Adequate cardiac function, defined as:

• No electrocardiogram (EKG) evidence of acute ischemia

• No EKG evidence of active, clinically significant conduction system abnormalities

• No EKG evidence of > grade 2 (> 480 ms) corrected QT (QTc) prolongation

• Prior to study entry, any EKG abnormality at screening not felt to put the patient at risk has to be documented by the investigator as not medically significant

• No uncontrolled angina or severe ventricular arrhythmias

• No clinically significant pericardial disease

• No history of myocardial infarction within 6 months prior to registration

• No class 3 or higher New York Heart Association congestive heart failure

• No strong inducers of cytochrome P450 (CYP) 3A4 or CYP1A2 or strong inhibitors of CYP3A4 or CYP1A2 within 14 days prior to registration

• Note: Ixazomib is a substrate of CYP3A4 and CYP1A2

• Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following:

• No history of acquired immunodeficiency syndrome (AIDS)-defining conditions or other HIV related illness

• Cluster of differentiation (CD)4+ cells nadirs > 350/mm^3 within 28 days prior to registration

• Treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3 within 28 days prior to registration

• Note: HIV+ patients who enroll on this study and are assigned to treatment with ixazomib may need to modify their anti-retroviral therapy prior to receiving protocol therapy if they are on strong inducers or potent inhibitors of cytochrome P450 3A4

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patients randomized to Arm 1 may opt to switch to the 3-drug regimen following disease progression; these patients must be re-registered to the study and meet the eligibility criteria below

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patient must have measurable disease or non-measurable disease after progression on pomalidomide + dexamethasone, defined as one or more of the following holding true:

• Measurable disease:

• Serum M-protein >= 0.5 g/dL and/or

• Urine M-protein >= 200 mg/24 hours and/or

• Involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio

• For non-measurable disease:

• Marrow burden of myeloma of at least 30%

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2):

• Women of childbearing potential:

** Must have a negative serum or urine pregnancy test within 72 hours prior to re-registration

** Must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, before starting pomalidomide

** Must agree to ongoing pregnancy testing

** Must agree to not become pregnant or breast feed a child during treatment on this protocol

• Men must practice complete abstinence or agree to use a condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy

• Note: All participants must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): ECOG performance status 0-2

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Platelet count >= 50 x 10^9/L

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Calc. creatinine clearance >= 30 mL/min

• Calculated utilizing the Cockcroft-Gault formula or 24-hour urine collection

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Total bilirubin < 1.5 x upper limits of normal (ULN)

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): AST and ALT < 2.5 x upper limits of normal (ULN)

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Note: G-CSF and platelet transfusions cannot be used to increase counts to meet eligibility criteria

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): =< grade 2 peripheral neuropathy

• RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): No strong inducers of cytochrome P450 (CYP) 3A4 or CYP1A2 or strong inhibitors of CYP3A4 or CYP1A2 * Note: Ixazomib is a substrate of CYP3A4 and CYP1A2

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma in Relapse
• Neoplasms, Plasma Cell

Intervention

Drug:
• pomalidomide
given PO
• ixazomib
given PO
• dexamethasone
given PO

Locations

Country	Name	City	State
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Hickman Cancer Center	Adrian	Michigan
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Regional Hospital	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Saint Charles Health System	Bend	Oregon
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	IHA Hematology Oncology Consultants-Canton	Canton	Michigan
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Caro Cancer Center	Caro	Michigan
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	University of Illinois	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Carle on Vermilion	Danville	Illinois
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	Central Ohio Breast and Endocrine Surgery	Gahanna	Ohio
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	East Carolina University	Greenville	North Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Saint Vincent Hospital Cancer Center at Marinette	Marinette	Wisconsin
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho
United States	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Saint Charles Hospital	Oregon	Ohio
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Rex Hematology Oncology Associates-Blue Ridge	Raleigh	North Carolina
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Nanticoke Memorial Hospital	Seaford	Delaware
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Mercy Saint Anne Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Munson Medical Center	Traverse City	Michigan
United States	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Mercy Hospital Washington	Washington	Missouri
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Metro Health Hospital	Wyoming	Michigan
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (4)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	Celgene Corporation, Millennium Pharmaceuticals, Inc., National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of Pomalidomide and Ixazomib, Determined According to Incidence of Dose Limiting Toxicity (DLT) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)	For this protocol, dose-limiting toxicity (DLT) will be defined by the following adverse events at least possibly related to study therapy: Grade 3 or higher non-hematologic toxicity, with the following exceptions: Alopecia is not expected but would not be considered a DLT. Nausea, vomiting and diarrhea will only be considered a DLT if it cannot be adequately managed with optimal supportive care. Grade 3 or 4 hyperglycemia due to dexamethasone will only be considered a DLT if it cannot be controlled with appropriate therapy Grade 4 hematologic toxicity, with the following exceptions: Grade 4 lymphopenia is expected with this regimen and will not be construed as a DLT. Grade 4 neutropenia will only be considered a DLT if it lasts longer than 7 days despite appropriate supportive care. Grade 4 thrombocytopenia will only be considered a DLT if it lasts longer than 7 days or is associated with greater then or equal to grade 3 bleeding event	28 days
Primary	Progression Free Survival (PFS) (Phase II)	progression-free survival (PFS), defined as the time from randomization to the date the International Myeloma Working Group (IMWG) criteria for disease progression is met. If a patient initiates another anti-cancer treatment prior to disease progression, they will be censored at the date of initiation of this treatment. Patients will be randomized to treatment using the Pocock-Simon algorithm balancing the distribution of the following stratification factors between the two treatment arms: 1) ISS 1-2 disease vs. ISS 3 disease (current ISS stage based off screening beta 2 microglobulin and albumin) 2) High risk cytogenetics features: yes vs. no High risk cytogenetics features include: del(1p), gain of 1q, t(4;14), t(14;16), t(14; 20), del(17p) 3) Prior treatment with a proteasome inhibitor: yes vs. no	3 years
Secondary	Incidence and Type of Dose Limiting Toxicities (DLTs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)	These events are reported in the adverse events section of this report.	44.5 months
Secondary	Incidence of Dose Reductions/Delays (Phase I)		39 months
Secondary	Overall Response Rate (ORR)	ORR is defined as partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) according to International Myeloma Working Group (IMWG) Uniform Response Criteria	3 years
Secondary	Clinical Benefit Rate (CBR)	Disease response status is based on the IMWG criteria being held for two consecutive evaluations at least 4 weeks apart. Clinical benefit rate (CBR) is defined as proportion of patients with minimal response (MR) and better according to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II)	3 years
Secondary	Disease Control Rate (DCR), Defined as Stable Disease (SD) and Better According to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II)	Proportion of patients that went two of more cycles of treatment without discontinuing treatment for progression or intolerability.	42 days
Secondary	Duration of Response (DOR), Calculated for All Patients Achieving an Objective Response, Partial Response (PR) or Better (Phase II)		Up to 3 years
Secondary	Overall Survival (OS) (Phase II)	Overall survival was analyzed from the time of registration to the date of death or last known date living. Due to median OS time not being reached due to lack of deaths at the time of this report by either arm, the 2 year OS rate has been reported. This analysis censors living patients at 2 years.	2 years
Secondary	Time to Next Treatment (TNT) (Phase II)		Up to 3 years post-registration
Secondary	Incidence, Type and Severity of Adverse Events, Graded According to National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE) Version 4.0 (Phase II)	The count of paitents that experenced an adverse event is reported in this section. A full table of these events is reported in the adverse event section of this report.	92 months
Secondary	Response Rates (Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Disease Control Rate (DCR) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)		Up to 3 years
Secondary	Progression Free Survival (PFS) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)		Up to 3 years post-registration (at crossover)
Secondary	Baseline Level of Perceived Fatigue and QOL, Assessed Using the Registration Fatigue/Uniscale Assessment Form (Phase II)	Pre-treatment patient-report of fatigue and overall quality of life (based on a 10-point Likert scale). A higher number indicates a better quality of life where 10 is the best outcome and 0 is the worst.	baseline