Alemtuzumab Plus Fludarabine and Melphalan With or Without Cyclosporine, Mycophenolate Mofetil, and Low-Dose Total-Body Irradiation Therapy Followed by Donor Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer

NCT ID: NCT00085449

Last Updated: 2019-11-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2007-01-31

Brief Summary

RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune system 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 cyclosporine and mycophenolate mofetil before transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and total-body irradiation before donor peripheral blood stem cell transplant and to see how well they work in treating patients with relapsed or refractory hematologic cancer.

Detailed Description

OBJECTIVES:

• Determine the ability of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and low-dose total body radiotherapy followed by haplotype-mismatched, KIR class I epitope-mismatched CD34-positive allogeneic peripheral blood stem cell transplantation to facilitate engraftment by day 35 post-transplantation in at least 85% of patients with relapsed, refractory, or poor-risk hematological malignancies.
• Determine the risk of graft-versus-host-disease in patients treated with these regimens.
• Determine, preliminarily, the efficacy of these regimens, in terms of progression-free survival, in these patients.
• Correlate outcomes, engraftment, and progression-free survival with the number of detectable alloreactive natural killer cell clones before transplantation and after engraftment in patients treated with these regimens.
• Determine immune reconstitution in patients treated with these regimens.

OUTLINE: This is a multicenter, pilot study. Patients are initially treated with conditioning regimen A. If adequate donor engraftment is not achieved, subsequent patients are treated with conditioning regimen B.

• Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2.
• Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1.

All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.

Patients are followed every 3 months for 1 year and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 14-56 patients (14-28 per regimen) will be accrued for this study.

Conditions

Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Regimen A + B

Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2.

Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1.

All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.

Patients are followed every 3 months for 1 year and then every 6 months for 5 years.

Group Type: EXPERIMENTAL

alemtuzumab

Intervention Type: BIOLOGICAL

cyclosporine

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

mycophenolate mofetil

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Interventions

alemtuzumab

Intervention Type: BIOLOGICAL

cyclosporine

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

mycophenolate mofetil

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Non-Hodgkin's lymphoma meeting 1 of the following criteria:

• Primarily refractory disease or in refractory relapse
• Relapsed disease after autologous stem cell transplantation
• Chemosensitive relapsed disease without CR to standard salvage therapy AND no option for autologous stem cell transplantation due to blood or marrow involvement or failure to harvest sufficient autologous stem cells
• Chronic lymphocytic leukemia meeting both of the following criteria:

• Stage III or IV disease
• Refractory to fludarabine
• Multiple myeloma meeting 1 of the following criteria:

• Primarily refractory disease or in refractory relapse
• Relapsed disease after autologous stem cell transplantation
• No relapsed disease < 6 months after autologous stem cell transplantation
• No available eligible HLA-matched (i.e., 5 of 6 or 6 of 6 antigen match for HLA-A, -B, and -DR loci) family donor by serological or molecular typing
• Available suitable family donor meeting the following criteria:

• Parent, sibling, or child of the recipient
• ≥ 16 years of age
• Identical for only one HLA haplotype (i.e., haploidentical) AND incompatible at the HLA-A, -B, -C, and -DR loci of the unshared haplotype by serological or molecular typing
• Mismatched with respect to KIR class I epitopes graft-vs-host directional activity

• Mismatching that predicts both graft-vs-host and host-vs-graft bi-directional activity eligible
• No mismatching that predicts only host-vs-graft directional activity

PATIENT CHARACTERISTICS:

Age

• 18 to 60

Performance status

• ECOG 0-1

Hepatic

• Bilirubin < 2 times upper limit of normal (ULN)
• AST and ALT < 2 times ULN

Renal

• Creatinine ≤ 2 mg/dL

Cardiovascular

• LVEF > 40% (corrected)

Pulmonary

• DLCO > 50% of predicted

Other

• No active infection requiring oral or IV antibiotics
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Concurrent corticosteroids allowed for adrenal failure, treatment of graft-vs-host disease, or as premedication during study
• No concurrent corticosteroids for antiemesis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sherif S. Farag, MD, PhD

Role: STUDY_CHAIR

Indiana University Melvin and Bren Simon Cancer Center

Locations

Moores UCSD Cancer Center

La Jolla, California, United States

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, United States

UCSF Comprehensive Cancer Center

San Francisco, California, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

Columbus, Ohio, United States

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

Other Identifiers

CALGB-100102

Identifier Type: -

Identifier Source: secondary_id

CDR0000370797

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-100102

Identifier Type: -

Identifier Source: org_study_id