Pentostatin, Cyclophosphamide, and Rituximab Followed By Campath-1H in Patients With Relapsed or Refractory B-Cell CLL

Leukemia Clinical Trial

Official title:

Phase II Trial of Pentostatin, Cyclophosphamide and Rituximab (PCR) Followed by Campath-1H for Previously Treated Relapsed or Refractory Patients With Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00074282
• Other study ID #: CDR0000343796
• Secondary ID: E2903
• Status: Completed
• Phase: Phase 2
• Start date: April 14, 2005
• Est. completion date: May 6, 2018

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as pentostatin, cyclophosphamide, and CAMPATH-1H work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well pentostatin, cyclophosphamide, rituximab, and CAMPATH-1H work in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia.

Description:

OBJECTIVES:

Primary

• Determine the objective response rate (complete remission, partial remission [PR], or nodular PR) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab (PCR) followed by CAMPATH-1H .

• Determine the presence of minimal residual disease in patients treated with this regimen who achieve a CR or nPR

Secondary

• Determine the toxicity of this regimen in these patients.

• Determine the overall and progression-free survival of patients treated with this regimen.

• Evaluate the number of patients who after PCR (or during PCR for PD), only achieve a PR, SD, or PD and who subsequently convert to a higher response category after CAMPATH-1H .

Exploratory

• Assess the angiogenic profile (i.e., secretion levels of pro- versus anti-angiogenic molecules) of CLL B cell clones as well as bone marrow angiogenesis (i.e., vascular density by immunohistochemistry) at baseline, after PCR, after CAMPATH-1H, every six months (serum only), and at time of response assessment (marrow).

• Determine the V_H gene mutation status and CD38 expression of the B-CLL clones at study entry and at the end of the therapy and assess the association between the VH gene mutation status and CD38 expression and clinical outcome.

• Determine surface phenotype (by flow cytometry) and genetic defects (by CLL FISH panel) information on CLL-B cell clones and associate with clinical outcome.

• Monitor the T-cell status by repertoire and flow cytometry analysis to determine the nature and extent of T-cell deficiency induced by the PCR and CAMPATH-1H treatment and assess any association with clinical outcome and toxicities.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: May 6, 2018
• Est. primary completion date: December 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria:

• Peripheral blood absolute lymphocyte count greater than 5,000/mm^3

• Lymphocytosis must comprise small to moderate size lymphocytes with no greater than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically

• Phenotypically characterized CLL defined by the following:

• Predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-cell markers (CD3 or CD2)

• B cell expresses either kappa or lambda light chains

• Surface immunoglobulin with low cell surface density expression

• Requires chemotherapy, as indicated by any of the following:

• Disease-related symptoms

• Weight loss of 10% or more within the past 6 months

• Extreme fatigue

• Fevers greater than 100.5°F for 2 weeks without evidence of infection

• Night sweats without evidence of infection

• Evidence of progressive marrow failure manifested by the development of or worsening anemia (hemoglobin no greater than 10 g/dL) and/or thrombocytopenia (platelet count no greater than 100,000/mm^3)

• Massive (i.e., greater than 6 cm below left costal margin) or progressive splenomegaly

• Massive nodes or clusters (i.e., greater than 10 cm in longest diameter) or progressive adenopathy

• Progressive lymphocytosis with an increase of greater than 50% over a 2-month period OR an anticipated doubling time of less than 6 months

• Demonstrated progression after at least 1 course of either an alkylating agent-based or purine nucleoside-based (e.g., fludarabine) regimen OR failed to achieve a meaningful response OR relapsed after prior therapy

• Patients who have relapsed after a pentostatin-based regimen are eligible provided the response was greater than 12 months prior to study entry

• 18 and over

• ECOG Performance Status 0-2

• Bilirubin no greater than 2 mg/dL (unless secondary to tumor, hemolysis, or Gilbert syndrome)

• Creatinine no greater than 2.0 mg/dL

• Creatinine clearance = 30 mL/min

• Negative pregnancy test

• Fertile patients must use 2 methods of effective contraception (including 1 barrier method) for at least 28 days before starting lenalidomide, while participating in the study, and for at least 28 days after discontinuation/stopping lenalidomide

• At least 8 weeks since prior rituximab

• At least 6 weeks since prior chemotherapy

• At least 1 year since prior pentostatin, cyclophosphamide, and rituximab (PCR) therapy

• PCR therapy at least 1 year prior to study entry allowed

Exclusion criteria:

• Bone marrow dysplasia related to prior therapy

• New York Heart Association class III or IV heart failure

• Prior lenalidomide

• Other malignancy within the past 2 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

• Pregnant or nursing

• Concurrent oral or IV antibiotics for active infection

Related Conditions & MeSH terms

• Leukemia

Intervention

Biological:
• rituximab

Drug:
• cyclophosphamide

• pentostatin

• Alemtuzumab

Locations

Country	Name	City	State
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Boulder Community Hospital	Boulder	Colorado
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Ochsner Health Center - Covington	Covington	Louisiana
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Swedish Medical Center	Englewood	Colorado
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Roger Maris Cancer Center at MeritCare Hospital	Fargo	North Dakota
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	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	North Colorado Medical Center	Greeley	Colorado
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	St. Rita's Medical Center	Lima	Ohio
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Saint Joseph Regional Medical Center	Mishawaka	Indiana
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	New Orleans Cancer Institute at Memorial Medical Center	New Orleans	Louisiana
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Beth Israel Medical Center - Petrie Division	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	North Suburban Medical Center	Thornton	Colorado
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Marshfield Clinic - Wausau Center	Wausau	Wisconsin
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Kay NE, Kim HT, Kempin S, et al.: Predictors of clinical outcome to pentostatin, cyclophosphamide and rituximab (PCR) followed by campath for relapsed/refractory CLL : a study of the Eastern Cooperative Oncology Group, E2903. [Abstract] Blood 112 (11): A-

Kempin S, Kay NE, Sun Z, et al.: Early results of pentostatin, cytoxan, rituximab (PCR) followed by CAMPATH-H (CA) for the treatment of relapse/refractory chronic lymphocytic leukemia (CLL) in ECOG protocol E2903. [Abstract] Blood 110 (11): A-3109, 2007.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate	Percent with response (CR, nPR, PR) with two-stage 90% confidence interval	8 weeks after Cycle 6
Primary	Molecular Complete Remission (MCR) Rate	Percent of patients who have MCR (clinical CR with flow negative and RT-PCR negative)	3 months post alemtuzumab
Secondary	Overall Survival (OS)	OS is defined as the time from registration until death from any cause.	Up to 5 years from registration
Secondary	Progression-free Survival (PFS)	PFS is defined as the time from registration until induction failure, institution of non-protocol therapy, relapse or death from any cause in the absence of relapse.	Up to 5 years from registration
Secondary	Number of Patients Who After PCR (or During PCR for PD), Only Achieve a PR, SD, or PD and Who Subsequently Convert to a Higher Response Category After Campath-1H		From re-registration up to 5 years (followed for response until progression)