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Rituximab, Cyclophosphamide, and Pegfilgrastim in Treating Patients With Leukemia or Non-Hodgkin's Lymphoma

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pegfilgrastim
Rituximab
Cyclophosphamide
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, B-cell chronic lymphocytic leukemia, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, Waldenstrom macroglobulinemia, prolymphocytic leukemia, stage I marginal zone lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II marginal zone lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III marginal zone lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia, stage IV marginal zone lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: One of the following B-cell leukemias or lymphomas, as defined by World Health Organization criteria: Chronic lymphocytic leukemia/small lymphocytic lymphoma B-cell prolymphocytic leukemia Lymphoplasmacytic leukemia Marginal zone lymphoma (splenic, extranodal, or nodal) Follicular lymphoma (grade 1 or 2) Mantle cell lymphoma No more than minimal (approximately 10%) morphologically identifiable cancer cells on bone marrow biopsy When cancer cells are morphologically difficult to distinguish from normal cells, flow cytometry must show no more than 10% identifiable cancer cells Must have received ≤ 12 months of prior cytotoxic therapy, achieving at least a partial response NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC ≥ 3,000/mm^3 Hemoglobin ≥ 10.0 g/dL Platelet count ≥ 75,000/mm^3 Serum creatinine ≤ 2.0 mg/dL Total bilirubin ≤ 2 mg/dL unless secondary to tumor AST or ALT < 2 times upper limit of normal Normal (≥ 45%) left ventricular cardiac ejection fraction (determined by echocardiogram or MUGA scan) DLCO > 50% predicted Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known sensitivity to E. coli-derived products (e.g. filgrastim [G-CSF], insulin, asparaginase, growth hormone, or recombinant interferon alfa-2b) or any treatment study drugs No active infections requiring oral or intravenous antibiotics No other second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix unless the malignancy was localized and treated or resected with > 90% probability of cure PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior anti-CD20 therapy allowed provided patient achieved a partial or complete response No concurrent steroids during rituximab administration

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

R-HiCy

Arm Description

Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.

Outcomes

Primary Outcome Measures

Engraftment
Median days to neutrophil and platelet recovery. Neutrophil recovery is defined as absolute neutrophil count >= 500 cells per microliter; platelet recovery is defined as untransfused platelet count >= 20 * 10^9 cells per liter.
Non-relapse Mortality
Number of participants who died for reasons related to protocol treatment.
Event-free Survival
Percentage of participants alive without disease relapse.

Secondary Outcome Measures

Full Information

First Posted
January 16, 2006
Last Updated
October 31, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00278161
Brief Title
Rituximab, Cyclophosphamide, and Pegfilgrastim in Treating Patients With Leukemia or Non-Hodgkin's Lymphoma
Official Title
Phase II Study of High Dose Cyclophosphamide and Rituximab in Low Grade and Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Monoclonal antibodies, such as rituximab, 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 cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving rituximab and cyclophosphamide together with pegfilgrastim may be effective in treating leukemia or non-Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well giving rituximab and cyclophosphamide together with pegfilgrastim works in treating patients with B-cell leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.
Detailed Description
OBJECTIVES: Determine the safety of high-dose cyclophosphamide, rituximab, and pegfilgrastim in patients with B-cell leukemia or low-grade or mantle cell lymphoma. Determine the molecular response rate in patients treated with this regimen. OUTLINE: This is an open-label study. Patients receive rituximab IV over 30-60 minutes on days 1, 4, 8,11, 45, and 52, cyclophosphamide IV over 1 hour on days 15-18, and pegfilgrastim subcutaneously on day 19 or 20 in the absence of unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 32 patients 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
stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, B-cell chronic lymphocytic leukemia, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, Waldenstrom macroglobulinemia, prolymphocytic leukemia, stage I marginal zone lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II marginal zone lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III marginal zone lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia, stage IV marginal zone lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
94 (Actual)

8. Arms, Groups, and Interventions

Arm Title
R-HiCy
Arm Type
Experimental
Arm Description
Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Intervention Type
Biological
Intervention Name(s)
Pegfilgrastim
Other Intervention Name(s)
Neulasta
Intervention Description
6 mg SQ 24-48 hours after last dose of cyclophosphamide.
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
375 mg/m^2/day on Days 1, 4, 8, 11, 45, and 52.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan, Cy, CTX
Intervention Description
50 mg/kg/day on Days 15, 16, 17, and 18.
Primary Outcome Measure Information:
Title
Engraftment
Description
Median days to neutrophil and platelet recovery. Neutrophil recovery is defined as absolute neutrophil count >= 500 cells per microliter; platelet recovery is defined as untransfused platelet count >= 20 * 10^9 cells per liter.
Time Frame
Up to 43 days
Title
Non-relapse Mortality
Description
Number of participants who died for reasons related to protocol treatment.
Time Frame
5 years
Title
Event-free Survival
Description
Percentage of participants alive without disease relapse.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: One of the following B-cell leukemias or lymphomas, as defined by World Health Organization criteria: Chronic lymphocytic leukemia/small lymphocytic lymphoma B-cell prolymphocytic leukemia Lymphoplasmacytic leukemia Marginal zone lymphoma (splenic, extranodal, or nodal) Follicular lymphoma (grade 1 or 2) Mantle cell lymphoma No more than minimal (approximately 10%) morphologically identifiable cancer cells on bone marrow biopsy When cancer cells are morphologically difficult to distinguish from normal cells, flow cytometry must show no more than 10% identifiable cancer cells Must have received ≤ 12 months of prior cytotoxic therapy, achieving at least a partial response NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC ≥ 3,000/mm^3 Hemoglobin ≥ 10.0 g/dL Platelet count ≥ 75,000/mm^3 Serum creatinine ≤ 2.0 mg/dL Total bilirubin ≤ 2 mg/dL unless secondary to tumor AST or ALT < 2 times upper limit of normal Normal (≥ 45%) left ventricular cardiac ejection fraction (determined by echocardiogram or MUGA scan) DLCO > 50% predicted Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known sensitivity to E. coli-derived products (e.g. filgrastim [G-CSF], insulin, asparaginase, growth hormone, or recombinant interferon alfa-2b) or any treatment study drugs No active infections requiring oral or intravenous antibiotics No other second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix unless the malignancy was localized and treated or resected with > 90% probability of cure PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior anti-CD20 therapy allowed provided patient achieved a partial or complete response No concurrent steroids during rituximab administration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lode J. Swinnen, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21756035
Citation
Gladstone DE, Bolanos-Meade J, Huff CA, Zahurak M, Flinn I, Borrello I, Luznik L, Fuchs E, Kasamon Y, Matsui W, Powell J, Levitsky H, Brodsky RA, Ambinder R, Jones RJ, Swinnen LJ. High-dose cyclophosphamide and rituximab without stem cell transplant: a feasibility study for low grade B-cell, transformed and mantle cell lymphomas. Leuk Lymphoma. 2011 Nov;52(11):2076-81. doi: 10.3109/10428194.2011.594191. Epub 2011 Jul 14.
Results Reference
result

Learn more about this trial

Rituximab, Cyclophosphamide, and Pegfilgrastim in Treating Patients With Leukemia or Non-Hodgkin's Lymphoma

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