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
18 Years
N/A
Both
Leukemia, Lymphoma
Trial Information
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
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.
Inclusion 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)
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Robert O. Dillman, MD, FACP
Investigator Role:
Study Chair
Investigator Affiliation:
Hoag Memorial Hospital Presbyterian
Authority:
United States: Federal Government
Study ID:
CDR0000258096
NCT ID:
NCT00049413
Start Date:
June 2002
Completion Date:
December 2005
Related Keywords:
- Leukemia
- Lymphoma
- 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
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Lymphoma
Name | Location |
|---|---|
| Hoag Cancer Center at Hoag Memorial Hospital Presbyterian | Newport Beach, California 92663 |
