Fludarabine and Cyclophosphamide Followed by Peripheral Stem Cell Transplant in Treating Patients With Leukemia or Lymphoma
Recruitment status was Active, not recruiting
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Purpose
RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
PURPOSE: This phase II trial is studying how well fludarabine and cyclophosphamide followed by peripheral stem cell transplant works in treating patients with leukemia or lymphoma.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia Lymphoma |
Drug: fludarabine phosphate Drug: Cyclophosphamide Biological: PBSC Drug: G-CSF Biological: Donor lymphocytes |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Minimal Ablation and Cellular Immune Therapy of Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-Grade Non-Hodgkin's Lymphoma, and Mantle Cell Lymphoma With Allogeneic Donor Stem Cells |
- Treatment-related mortality within the first 6 months post-transplant [ Time Frame: 6 months post chemo initiation ] [ Designated as safety issue: Yes ]
- Response [ Time Frame: 6 months & 12 months ] [ Designated as safety issue: No ]
- Percentage of patients achieving complete donor chimerism or mixed donor chimerism [ Time Frame: 90 days post transplant ] [ Designated as safety issue: No ]
- Survival [ Time Frame: 5 years post study entry ] [ Designated as safety issue: No ]Disease free and overall survival will be assessed
| Enrollment: | 47 |
| Study Start Date: | February 2001 |
| Estimated Study Completion Date: | October 2011 |
| Primary Completion Date: | January 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Allogeneic Stem Cell Tx
minimal ablation and cellular immune therapy with allogeneic donor stem cell therapy
|
Drug: fludarabine phosphate
30 mg/sq m/day IV infusion for 5 days (Days -7 thru -3)
Drug: Cyclophosphamide
1 g/sq m/day IV infusion x 3 days (Days -5 thru -3)
Biological: PBSC
2-8,000,000/kg CD34+ cells via infusion on Day 0
Drug: G-CSF
5 ug/kg/day subQ injection until ANC > 1000/uL for 3 days beginning Day 5
Biological: Donor lymphocytes
10,000,000 CD3+ cells/kg via infusion
|
Detailed Description:
OBJECTIVES:
- Determine the feasibility of fludarabine and cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation, in terms of 6-month treatment-related mortality, in patients with chronic lymphocytic leukemia, prolymphocytic leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.
- Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
- Determine the time to disease progression in patients responding to this regimen.
- Determine the percentage of donor chimerism achieved in patients treated with this regimen.
- Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Determine the toxic effects of this regimen in these patients.
- Determine the overall survival and disease-free survival of patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1 to 2 hours on days -5 to -3. Patients undergo allogeneic peripheral blood stem cell transplantation on days 0-1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 5 and continuing until blood counts recover.
Patients with no signs of active graft-versus host disease and stable or progressive disease receive donor lymphocytes IV over 2 hours beginning after day 120. Patients may receive a total of 3 infusions at least 8 weeks apart if disease remains stable or progressive.
Patients are followed every 3 months for 2 years and then every 6 months for 5 years.
PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | up to 69 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
One of the following histologically confirmed diagnoses:
Chronic lymphocytic leukemia
- Absolute lymphocytosis greater than 5,000/mm^3
- Morphologically mature lymphocytes with less than 55% prolymphocytes
- Lymphocyte phenotypic expression of CD19 and CD5
Failed at least 1 prior regimen
- Progressive lymphocytosis with more than 50% increase in peripheral lymphocytosis or a progressive lymph node or spleen enlargement (at least 25% enlargement or the appearance of new lymph nodes) that persists for at least 4 weeks despite concurrent or prior drug treatment OR
- At least 1 of the following high-risk factors and not in first complete remission
= 17p deletion = 11q deletion
- Unmutated VH gene status
p53 mutations
Prolymphocytic leukemia (PLL)
- Absolute lymphocytosis greater than 5,000/mm^3
- Morphologically mature lymphocytes with more than 55% prolymphocytes
Low-grade non-Hodgkin's lymphoma
- Small lymphocytic lymphoma
- Follicular center lymphoma (grade I or II)
- Diffuse (predominately small cell type)
- Marginal zone, B-cell lymphoma
- No transformed lymphoma
- Failure of at least 1 prior regimen OR
- At least 3 of the following risk factors:
- Over 60 years of age
- Performance status greater than 1
- LDH greater than normal
- More than 1 site of extranodal disease
Disease stage III or IV
Mantle cell lymphoma
- Any stage
- Ineligible for protocol CALGB-59908
- At least 1 prior treatment regimen
- At least 1 of the following:
- Immunophenotypic expression of CD5 and CD19 and absence of CD23
- Cytogenetic analysis with presence of t(11;14)
- Overexpression of cyclin D1
Rearrangement of BCL1 gene
Responsive or stable disease to most recent prior therapy
- Prior therapy for PLL not required
Must have HLA identical sibling (6/6) donor by serologic typing (A, B, DR)
- No syngeneic donors
- No age restriction 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:
Age:
- Under 70
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Granulocyte count at least 500/mm^3*
- Platelet count at least 50,000/mm^3* NOTE: *Unless attributable to disease
Hepatic:
- Bilirubin no greater than 3 times upper limit of normal (ULN)*
- AST no greater than 3 times ULN* NOTE: *Unless attributable to disease
Renal:
- Creatinine clearance at least 40 mL/min, unless attributable to disease
Cardiovascular:
- LVEF at least 30% by MUGA
Pulmonary:
- DLCO greater than 40%
- No symptomatic pulmonary disease
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No uncontrolled diabetes mellitus
- No active serious infection
- No known hypersensitivity to E. coli-derived products
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior autologous transplantation
Chemotherapy:
- At least 4 weeks since prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- At least 4 weeks since prior radiotherapy
Surgery:
- At least 4 weeks since prior surgery
Contacts and Locations| United States, California | |
| Rebecca and John Moores UCSD Cancer Center | |
| La Jolla, California, United States, 92093-0658 | |
| Veterans Affairs Medical Center - San Diego | |
| San Diego, California, United States, 92161 | |
| UCSF Comprehensive Cancer Center | |
| San Francisco, California, United States, 94115 | |
| United States, Delaware | |
| Beebe Medical Center | |
| Lewes, Delaware, United States, 19958 | |
| CCOP - Christiana Care Health Services | |
| Newark, Delaware, United States, 19713 | |
| St. Francis Hospital | |
| Wilmington, Delaware, United States, 19805 | |
| United States, Iowa | |
| Holden Comprehensive Cancer Center at University of Iowa | |
| Iowa City, Iowa, United States, 52242 | |
| United States, Maryland | |
| Union Hospital Cancer Center at Union Hospital | |
| Elkton MD, Maryland, United States, 21921 | |
| United States, Massachusetts | |
| UMASS Memorial Cancer Center - University Campus | |
| Worcester, Massachusetts, United States, 01655 | |
| United States, New Jersey | |
| Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees | |
| Voorhees, New Jersey, United States, 08043 | |
| United States, New York | |
| Roswell Park Cancer Institute | |
| Buffalo, New York, United States, 14263-0001 | |
| Elmhurst Hospital Center | |
| Elmhurst, New York, United States, 11373 | |
| Queens Cancer Center of Queens Hospital | |
| Jamaica, New York, United States, 11432 | |
| Mount Sinai Medical Center | |
| New York, New York, United States, 10029 | |
| United States, North Carolina | |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | |
| Chapel Hill, North Carolina, United States, 27599-7295 | |
| Wake Forest University Comprehensive Cancer Center | |
| Winston-Salem, North Carolina, United States, 27157-1096 | |
| United States, Ohio | |
| Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University | |
| Columbus, Ohio, United States, 43210-1240 | |
| United States, Pennsylvania | |
| Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital | |
| Pittsburgh, Pennsylvania, United States, 15224-1791 | |
| United States, Virginia | |
| Massey Cancer Center at Virginia Commonwealth University | |
| Richmond, Virginia, United States, 23298-0037 | |
| Study Chair: | Thomas C. Shea, MD | UNC Lineberger Comprehensive Cancer Center |
More Information
Additional Information:
Publications:
| Responsible Party: | Monica M Bertagnolli, Cancer and Leukemia Group B |
| ClinicalTrials.gov Identifier: | NCT00006252 History of Changes |
| Other Study ID Numbers: | CDR0000068185, U10CA031946, CALGB-109901 |
| Study First Received: | September 11, 2000 |
| Last Updated: | April 1, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by Cancer and Leukemia Group B:
|
refractory chronic lymphocytic leukemia stage I grade 1 follicular lymphoma stage I grade 2 follicular lymphoma stage I adult diffuse small cleaved cell lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III adult diffuse small cleaved cell lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV adult diffuse small cleaved cell lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent adult diffuse small cleaved cell lymphoma prolymphocytic leukemia stage I mantle cell lymphoma |
contiguous stage II grade 1 follicular lymphoma contiguous stage II grade 2 follicular lymphoma contiguous stage II adult diffuse small cleaved cell lymphoma contiguous stage II mantle cell lymphoma noncontiguous stage II grade 1 follicular lymphoma noncontiguous stage II grade 2 follicular lymphoma noncontiguous stage II adult diffuse small cleaved cell lymphoma noncontiguous stage II mantle cell lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma recurrent mantle cell lymphoma contiguous stage II small lymphocytic lymphoma contiguous stage II marginal zone lymphoma noncontiguous stage II small lymphocytic lymphoma noncontiguous stage II marginal zone lymphoma |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Prolymphocytic Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cyclophosphamide |
Fludarabine monophosphate Fludarabine Vidarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antimetabolites, Antineoplastic |
ClinicalTrials.gov processed this record on May 23, 2013