S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

Leukemia Clinical Trial

Official title:

S0910, A Phase II Study of Epratuzumab (NSC-716711) in Combination With Cytarabine and Clofarabine for Patients With Relapsed or Refractory Ph- Negative Precursor B-Cell Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00945815
• Other study ID #: S0910
• Secondary ID: S0910U10CA032102
• Status: Completed
• Phase: Phase 2
• First received: July 23, 2009
• Last updated: October 3, 2017
• Start date: September 2010
• Est. completion date: August 2017

Study information

• Verified date: October 2017
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies, such as epratuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cytarabine and clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving epratuzumab together with cytarabine and clofarabine may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects and how well giving epratuzumab together with cytarabine and clofarabine works in treating patients with relapsed or refractory acute lymphoblastic leukemia.

Description:

OBJECTIVES:

• To test whether the complete remission (CR) rate (CR and incomplete CR) in adult patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia is sufficiently high after treatment with cytarabine, clofarabine, and epratuzumab to warrant further investigation.

• To estimate the frequency and severity of toxicities associated with the dosing schedule of cytarabine, clofarabine, and epratuzumab used in this study.

• To investigate, preliminarily, the effect of laboratory correlates (minimal post-treatment residual disease) and cytogenetic factors on prognosis in this patient population. (Not reported here due to limited MRD data)

OUTLINE: This is a multicenter study.

Patients receive cytarabine IV over 2 hours on days 1-5, clofarabine IV over 1 hour on days 2-6, and epratuzumab IV over at least 1 hour on days 7, 14, 21, and 28 in the absence of disease progression or unacceptable toxicity*.

NOTE: * Prophylactic intrathecal methotrexate is required for patients < 22 years of age, and is recommended (but not required) for patients ≥ 22 years of age.

Blood samples, bone marrow samples, and/or tumor tissue samples may be collected for further laboratory analysis.

Patients are followed up every 3 months for 2 years, then annually for 3 years (until 5 years after registration).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: August 2017
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Morphologically confirmed precursor B-cell acute lymphoblastic leukemia (ALL) (non T-cell)

• Must have evidence of disease in bone marrow or peripheral blood

• Immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T cell, or mixed B/T cell)

• Must have = 5% lymphoblasts present in the blood or bone marrow

• At least 20% of marrow and/or peripheral blood lymphoblasts must be CD22+ by flow cytometry

• Co-expression of myeloid antigens (CD13 and CD33) allowed

• Patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible

• Philadelphia (Ph) chromosome-negative disease

• Patients with unknown Ph status by cytogenetics or FISH and unknown BCR/ABL status by PCR are eligible for study registration, but must be removed from study therapy if found to be Ph+ or BCR/ABL+ after study registration

• Refractory to a standard induction regimen that included vincristine and prednisone or high-dose cytarabine or mitoxantrone OR relapsed after successful prior induction therapy

• Any number of prior induction therapies or any number of remissions achieved are allowed

• No M0 acute myeloid leukemia, mixed lineage leukemia, or L3 (Burkitt) leukemia

• No active CNS involvement by clinical evaluation

• Patients with a documented history of CNS involvement of ALL or with clinical signs or symptoms consistent with CNS involvement of ALL must undergo a lumbar puncture that is negative for CNS involvement of ALL

• Patients < 22 years of age must be willing to receive prophylactic intrathecal chemotherapy

• Must be registered on SWOG-9007 "Cytogenetic Studies in Leukemia Patients" (closed as of 07/01/2010)

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Serum creatinine = 1.0 mg/dL OR glomerular filtration rate > 60 mL/min

• AST and ALT = 2.5 times upper limit of normal (ULN)

• Alkaline phosphatase = 2.5 times ULN

• Bilirubin = 1.5 times ULN

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for = 6 months after completion of study treatment

• HIV-positive patients are eligible (at the discretion of the investigator) provided the following criteria are met:

• No history of AIDS-defining conditions

• CD4 cell count > 350/mm³

• If on antiretroviral agents, must not include zidovudine or stavudine

• Willing to receive prophylaxis for pneumocystis jirovecii pneumonia during study therapy (regardless of CD4 cell count) until the CD4 cell count is > 200/mm³ after completion of study treatment

• Prior malignancy (other than ALL) allowed provided it is in remission and there are no plans to treat the malignancy at the time of study registration

• No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as exhibiting ongoing signs or symptoms related to the infection with no improvement despite appropriate antibiotics or other treatment

• No neuropathy (cranial, motor or sensory) = grade 2

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Any number of prior therapies allowed

• More than 90 days since prior allogeneic bone marrow transplant (BMT)

• No concurrent immunosuppression therapy for the treatment of graft-vs-host disease (GVHD)

• No acute GVHD = grade 2, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity

• Prior autologous BMT allowed

• No concurrent immunosuppression therapy for the treatment of GVHD

• More than 14 days since prior chemotherapy, investigational agents, or major surgery and recovered

• Maintenance therapy with steroids, vincristine, and/or anti-metabolite agents, including but not limited to, mercaptopurine, thioguanine, and methotrexate allowed

• Concurrent hydroxyurea to reduce WBC to a reasonable level (as deemed by the treating physician) allowed

• No prior clofarabine or epratuzumab

• No other concurrent cytotoxic therapy or investigational therapy

• No concurrent alternative medications (e.g., herbal or botanical medications for anticancer purposes)

• Concurrent participation on SWOG-S9910 "Leukemia Centralized Reference Laboratories and Tissue Repositories, Ancillary" allowed (closed as of 07/01/2010)

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• epratuzumab

Drug:
• clofarabine

• cytarabine

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	American Fork Hospital	American Fork	Utah
United States	Island Hospital Cancer Care Center at Island Hospital	Anacortes	Washington
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Hematology-Oncology Clinic	Baton Rouge	Louisiana
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Highline Medical Center Cancer Center	Burien	Washington
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina
United States	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina
United States	St. Peter's Hospital	Helena	Montana
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital	Houston	Texas
United States	Veterans Affairs Medical Center - Houston	Houston	Texas
United States	Swedish Medical Center - Issaquah Campus	Issaquah	Washington
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Logan Regional Hospital	Logan	Utah
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Cancer Center	Sacramento	California
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	LDS Hospital	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	North Puget Oncology at United General Hospital	Sedro-Woolley	Washington
United States	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology, PS	Spokane	Washington
United States	Stanford Cancer Center	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Remission	Complete remission (CR) is defined as: <5% marrow aspirate blasts. Blasts can be >=5% if the blasts are found to be myeloid and there is no evidence of lymphoblasts by flow cytometry or immunostaining. Neutrophils >= 1000/mcl; platelets >100,000/mcl; and no blasts in the peripheral blood. C1 Extramedullary disease status as defined in the protocol. Complete remission with incomplete platelet recovery (CRi) is same as CR but platelet count may be <=100,000/mcl and/or ANC may be <1,000/mcl.	After induction therapy was completed (1 or 2 months)
Secondary	Number of Patients With Grade 3 Through 5 Treatment-Related Adverse Events	Only adverse events that are possibly, probably or definitely related to study drug are reported. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.	Up to 5 years