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

This study has been completed.
Sponsor:
Collaborator:
Cancer Biotherapy Research Group
Information provided by:
Hoag Memorial Hospital Presbyterian
ClinicalTrials.gov Identifier:
NCT00049413
First received: November 12, 2002
Last updated: May 10, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Biological: rituximab
Drug: cyclophosphamide
Drug: pentostatin
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoag Memorial Hospital Presbyterian:

Study Start Date: June 2002
Study Completion Date: December 2005
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049413

Locations
United States, California
Hoag Cancer Center at Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States, 92658
Sponsors and Collaborators
Hoag Memorial Hospital Presbyterian
Cancer Biotherapy Research Group
Investigators
Study Chair: Robert O. Dillman, MD, FACP Hoag Memorial Hospital Presbyterian
  More Information

Additional Information:
No publications provided

Responsible Party: Robert O. Dillman, MD, Hoag Memorial Hospital Presbyterian
ClinicalTrials.gov Identifier: NCT00049413     History of Changes
Other Study ID Numbers: CDR0000258096, CBRG-NIP-0201, NCI-V02-1712, SUPEREN-CBRG-NIP-0201
Study First Received: November 12, 2002
Last Updated: May 10, 2011
Health Authority: United States: Federal Government

Keywords provided by Hoag Memorial Hospital Presbyterian:
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Pentostatin
Rituximab
Adenosine Deaminase Inhibitors
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014