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Combination Chemotherapy and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
cyclophosphamide
pentostatin
Sponsored by
Hoag Memorial Hospital Presbyterian
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, recurrent small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small B-cell lymphocytic lymphoma (SLL) with the following: Lymph node biopsy interpreted as SLL or consistent with CLL or all of the following: Peripheral lymphocyte count greater than 5,000/mm^3 with small to moderate peripheral lymphocytes and no more than 55% prolymphocytes Bone marrow aspirate containing at least 30% lymphoid cells Immunophenotypic evaluation of peripheral blood lymphocytes demonstrating monoclonality of B lymphocytes with all of the following: CD19 or CD20 coexpressed with CD5 antigen in the absence of other pan-T- cell markers (e.g., CD2 or CD3) Expression of CD23 on CLL cells or Dim B-cell expression of kappa or lambda light chains Measurable disease with any of the following: 1 or more lymph nodes at least 1.5 cm by CT scan Splenomegaly by CT scan Peripheral lymphocyte count greater than 5,000/mm3 with coexpression of CD5 and B-cell markers Bone marrow aspirate with at least 30% lymphoid cells No mantle cell lymphoma PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 2 years Hematopoietic See Disease Characteristics No immune thrombocytopenia No hemolytic anemia Hepatic Bilirubin no greater than 3 times upper limit of normal (ULN) SGOT no greater than 3 times ULN (unless due to hemolysis or CLL) No hepatitis Renal Creatinine no greater than 1.5 times ULN Cardiovascular No cardiac dysfunction No New York Heart Association class III or IV heart disease No myocardial infarction within the past month Other HIV negative No active acute or chronic infection No immunosuppressive diseases No autoimmune disorder No secondary malignancy that is projected to limit life expectancy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy See Chemotherapy No prior rituximab At least 4 weeks since prior biologic therapy Chemotherapy At least 4 weeks since prior chemotherapy No prior combination chemotherapy and rituximab or other antibody therapy No prior combination chemotherapy comprising an alkylating agent and a purine nucleoside analog (i.e., cyclophosphamide or chlorambucil in combination with fludarabine, cladribine, or pentostatin) No prior pentostatin Endocrine therapy At least 4 weeks since prior corticosteroids No concurrent supra-physiologic doses of corticosteroids Radiotherapy At least 4 weeks since prior radiotherapy Surgery At least 4 weeks since prior major surgery Other No concurrent immunosuppressive therapy (e.g., cyclosporine)

Sites / Locations

  • Hoag Cancer Center at Hoag Memorial Hospital Presbyterian

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 12, 2002
Last Updated
May 10, 2011
Sponsor
Hoag Memorial Hospital Presbyterian
Collaborators
Cancer Biotherapy Research Group
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1. Study Identification

Unique Protocol Identification Number
NCT00049413
Brief Title
Combination Chemotherapy and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
Official Title
Pentostatin, Cyclophosphamide And Rituximab (PCR) For B-Cell Chronic Lymphocytic Leukemia (CLL) And Small B-Cell Lymphocytic Lymphoma (SLL): Four Phase II Trials With Patient Stratification Based On Prior Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2011
Overall Recruitment Status
Completed
Study Start Date
June 2002 (undefined)
Primary Completion Date
December 2004 (Actual)
Study Completion Date
December 2005 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Hoag Memorial Hospital Presbyterian
Collaborators
Cancer Biotherapy Research Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies 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 cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining pentostatin and cyclophosphamide with rituximab in treating patients who have chronic lymphocytic leukemia or lymphocytic lymphoma.
Detailed Description
OBJECTIVES: Determine the efficacy of pentostatin, cyclophosphamide, and rituximab, in terms of response rate, time to treatment failure, time to disease progression, durability of response, and overall survival, in patients with B-cell chronic lymphocytic leukemia or small B-cell lymphocytic lymphoma. Determine the safety of this regimen, in terms of acute, subacute, and chronic toxicity, in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (no prior chemotherapy for chronic lymphocytic leukemia vs prior purine analog-based therapy [fludarabine or cladribine] but no alkylator therapy vs prior alkylator-based therapy [chlorambucil or cyclophosphamide] but no prior purine analog therapy vs prior therapy with alkylators and purine analogs, but not as combination therapy). First course: Patients receive rituximab IV over 1-4 hours on days 1-3 and pentostatin IV over 10-30 minutes and cyclophosphamide IV over 30-60 minutes on day 1. All subsequent courses: Patients receive rituximab IV over 60 minutes, pentostatin IV over 10-30 minutes, and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 5 years. PROJECTED ACCRUAL: A total of 160-240 patients (40-60 per stratum) will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, recurrent small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
pentostatin

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small B-cell lymphocytic lymphoma (SLL) with the following: Lymph node biopsy interpreted as SLL or consistent with CLL or all of the following: Peripheral lymphocyte count greater than 5,000/mm^3 with small to moderate peripheral lymphocytes and no more than 55% prolymphocytes Bone marrow aspirate containing at least 30% lymphoid cells Immunophenotypic evaluation of peripheral blood lymphocytes demonstrating monoclonality of B lymphocytes with all of the following: CD19 or CD20 coexpressed with CD5 antigen in the absence of other pan-T- cell markers (e.g., CD2 or CD3) Expression of CD23 on CLL cells or Dim B-cell expression of kappa or lambda light chains Measurable disease with any of the following: 1 or more lymph nodes at least 1.5 cm by CT scan Splenomegaly by CT scan Peripheral lymphocyte count greater than 5,000/mm3 with coexpression of CD5 and B-cell markers Bone marrow aspirate with at least 30% lymphoid cells No mantle cell lymphoma PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 2 years Hematopoietic See Disease Characteristics No immune thrombocytopenia No hemolytic anemia Hepatic Bilirubin no greater than 3 times upper limit of normal (ULN) SGOT no greater than 3 times ULN (unless due to hemolysis or CLL) No hepatitis Renal Creatinine no greater than 1.5 times ULN Cardiovascular No cardiac dysfunction No New York Heart Association class III or IV heart disease No myocardial infarction within the past month Other HIV negative No active acute or chronic infection No immunosuppressive diseases No autoimmune disorder No secondary malignancy that is projected to limit life expectancy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy See Chemotherapy No prior rituximab At least 4 weeks since prior biologic therapy Chemotherapy At least 4 weeks since prior chemotherapy No prior combination chemotherapy and rituximab or other antibody therapy No prior combination chemotherapy comprising an alkylating agent and a purine nucleoside analog (i.e., cyclophosphamide or chlorambucil in combination with fludarabine, cladribine, or pentostatin) No prior pentostatin Endocrine therapy At least 4 weeks since prior corticosteroids No concurrent supra-physiologic doses of corticosteroids Radiotherapy At least 4 weeks since prior radiotherapy Surgery At least 4 weeks since prior major surgery Other No concurrent immunosuppressive therapy (e.g., cyclosporine)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert O. Dillman, MD, FACP
Organizational Affiliation
Hoag Memorial Hospital Presbyterian
Official's Role
Study Chair
Facility Information:
Facility Name
Hoag Cancer Center at Hoag Memorial Hospital Presbyterian
City
Newport Beach
State/Province
California
ZIP/Postal Code
92658
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Combination Chemotherapy and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

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