Clinical trial NCT00278161: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-18
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Engraftment
timeFrame: Up to 43 days
measure: Non-relapse Mortality
timeFrame: 5 years
measure: Event-free Survival
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Lode J. Swinnen, MD
role: STUDY_CHAIR
References:
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.