Chemotherapy, Total-Body Irradiation, Rituximab, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00425802

Purpose

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor 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. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving rituximab before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects and how well giving chemotherapy and radiation therapy together with rituximab and donor stem cell transplant works in treating patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

Condition	Intervention	Phase
Leukemia Lymphoma	Biological: anti-thymocyte globulin Biological: filgrastim Biological: graft-versus-tumor induction therapy Biological: rituximab Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Radiation: total-body irradiation	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Non-Myeloablative Conditioning Regimen With Peri-Transplant Rituximab and the Transplantation of Hematopoietic Stem Cells From HLA-Compatible Related or Unrelated Donors in Patients With B Cell Lymphoid Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Ataxia Telangiectasia Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Cyclophosphamide Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Mycophenolate mofetil hydrochloride Filgrastim Mycophenolate Mofetil Rituximab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall and event-free survival at 1 year [ Designated as safety issue: No ]

Secondary Outcome Measures:

Speed of neutrophil and platelet recovery [ Designated as safety issue: No ]
Incidence and speed of donor-derived engraftment [ Designated as safety issue: No ]
Incidence and severity of acute graft versus host disease (GVHD) at 100 days [ Designated as safety issue: No ]
Incidence and severity of chronic GVHD at 1 year [ Designated as safety issue: No ]
Correlation of incidence of serious infectious complications with immune recovery [ Designated as safety issue: No ]
Response to treatment [ Designated as safety issue: No ]
Incidence of transplant-related mortality at 100 and 180 days [ Designated as safety issue: No ]
Incidence of malignant relapse or disease progression at 1 and 2 years [ Designated as safety issue: No ]
Probabilities of overall and event-free survival at 2 years [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	November 2006
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the overall and event-free survival at 1 year in patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with a nonmyeloablative conditioning regimen, rituximab, and allogeneic hematopoietic stem cell transplantation.

Secondary

Determine the speed of neutrophil and platelet recovery in patients treated with this regimen.
Determine the incidence and speed of donor-derived engraftment in these patients.
Determine the incidence and severity of acute graft versus host disease (GVHD) at 100 days in patients treated with this regimen.
Determine the incidence and severity of chronic GVHD at 1 year in patients treated with this regimen.
Correlate the incidence of serious infectious complications with immune recovery in patients treated with this regimen.
Determine the response in patients treated with this regimen.
Determine the incidence of transplant-related mortality at 100 and 180 days in these patients.
Determine the incidence of malignant relapse or disease progression at 1 and 2 years in these patients.
Determine the probabilities of overall and event-free survival at 2 years in patients treated with this regimen.

OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched unrelated or single HLA allele-disparate related or unrelated).

Rituximab therapy: Patients receive rituximab IV on day -8 or -7 and on days 21, 28, 35, and 42.
Nonmyeloablative conditioning: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2, cyclophosphamide IV on day -6, and anti-thymocyte globulin (ATG)* IV over 4-6 hours on days -3 and/or -2. Patients undergo total-body irradiation on day -1.

NOTE: *Patients with HLA-matched sibling donors do not receive ATG.

Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo filgrastim (G-CSF)-mobilized allogeneic HSCT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
Graft versus host disease prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally twice daily on days -3 to 100 followed by a taper and mycophenolate mofetil IV or orally twice daily on days -3 to 45 followed by a taper, in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- CD20-positive aggressive B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes:
  - Diffuse large cell lymphoma*, meeting 1 of the following criteria:
    - Relapsed disease after initial therapy, but failed to mobilize or had bone marrow involvement and therefore is not suitable for an autologous stem cell transplantation
    - High-intermediate- or high-risk second-line, age-adjusted International Prognostic Index score and in second complete remission (CR) or partial remission (PR) after autologous stem cell transplantation
    - Failed prior autologous stem cell transplantation and in PR or better after salvage chemotherapy
  - Large cell transformation of indolent NHL or chronic lymphocytic leukemia (CLL), meeting the following criteria:
    - In CR or PR of the large cell component of disease after salvage chemotherapy or autologous stem cell transplantation
  - Mantle cell lymphoma*, meeting 1 of the following criteria:
    - High-risk disease (e.g., p53 positivity) and in first CR or PR after initial therapy
    - Relapsed disease after initial therapy and in second or third CR or PR after salvage chemotherapy NOTE: *No progressive disease at allograft work-up
- CD20-positive indolent NHL (e.g., follicular lymphoma, small cell lymphoma, or marginal zone NHL) OR CLL
  - Second or subsequent progression (pre-allograft cytoreduction necessary, but CR or PR not required)
Relapsed disease must be biopsy-proven
Must have received pre-allograft salvage chemotherapy, including 1 of the following:
- Single autologous stem cell transplantation using high-dose chemotherapy conditioning within the past 120 days
- At least 2 courses of intensive combination chemotherapy (e.g., RICE [rituximab, ifosfamide, carboplatin, etoposide]), according to diagnosis, within the past 60 days
- If further combination chemotherapy is not appropriate (for heavily pretreated CLL patients), 2-3 courses of single-agent, intermediate-dose cyclophosphamide is required within the past 60 days
HLA-compatible related or unrelated donor available
- HLA-matched ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution typing
  - One allele mismatch allowed

PATIENT CHARACTERISTICS:

Karnofsky performance status 70-100%
Creatinine < 1.2 mg/mL OR creatinine clearance ≥ 50 mL/min
Bilirubin < 2.5 mg/dL
AST and ALT ≤ 3 times upper limit of normal (unless benign congenital hyperbilirubinemia is present)
Spirometry and corrected DLCO ≥ 50% of normal
LVEF ≥ 40%
Albumin ≥ 2.5 g/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active uncontrolled infection, including active infection with Aspergillus or other mold
No HIV infection
No hepatitis B antibody or antigen positivity

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior allogeneic transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00425802

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Hugo R. Castro-Malaspina, MD 212-639-8197

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Hugo R. Castro-Malaspina, MD	Memorial Sloan-Kettering Cancer Center
Principal Investigator:	Juliet Barker, MBBS	Memorial Sloan-Kettering Cancer Center
Principal Investigator:	Craig Moskowitz, MD	Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Hugo R. Castro-Malaspina )
Study ID Numbers:	CDR0000525951, MSKCC-06150
Study First Received:	January 19, 2007
Last Updated:	October 14, 2009
ClinicalTrials.gov Identifier:	NCT00425802 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

noncontiguous stage II adult diffuse large cell lymphoma
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
B-cell chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
noncontiguous stage II mantle cell lymphoma
recurrent mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
recurrent grade 1 follicular lymphoma

recurrent 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
noncontiguous stage II small lymphocytic lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
splenic marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Vidarabine
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Mycophenolic Acid
Cyclophosphamide
Antibiotics, Antineoplastic
Cyclosporins
Lymphoma, B-Cell

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Antifungal Agents
Therapeutic Uses
Lymphoma, Large-Cell, Immunoblastic
Mycophenolate mofetil
Dermatologic Agents
Alkylating Agents
Lymphoma
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Rituximab
Enzyme Inhibitors
Fludarabine monophosphate

ClinicalTrials.gov processed this record on November 27, 2009