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

Lymphoma Clinical Trial

Official title:

A Trial of Reduced Intensity Conditioning and Transplantation of Haplotype Mismatched and KIR Class I Epitope-Mismatched Highly Purified CD34 Cells

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00085449
• Other study ID #: CALGB-100102
• Secondary ID: CALGB-100102CDR0
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: May 2006
• Est. completion date: January 2007

Study information

• Verified date: November 2019
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed hematological malignancy of 1 of the following types:

• Acute myeloid leukemia meeting at least 1 of the following criteria:

• Poor-risk cytogenetics, including -5, 5q-, -7, 7q-, 11q23, and Philadelphia (Ph) chromosome-positive in first or subsequent complete remission (CR)

• Relapsed or primary refractory disease with = 10% blasts in the peripheral blood and = 20% blasts in the bone marrow

• Standard-risk cytogenetics in second CR AND autologous transplantation is not feasible

• Standard-risk cytogenetics in third or subsequent CR

• Acute lymphoblastic leukemia meeting 1 of the following criteria:

• Second or subsequent CR

• High-risk cytogenetics, including Ph chromosome-positive and t(4:11) in first CR

• Relapsed or primarily refractory disease with = 10% blasts in the peripheral blood and = 20% blasts in the bone marrow

• High-risk myelodysplasia

• International Prognostic Scoring System Score = 2.5

• Chronic myeloid leukemia (CML)* with an inadequate response to imatinib meeting 1 of the following criteria:

• Second or subsequent chronic phase

• Accelerated phase NOTE: *Patients with CML in blast crisis (> 30% promyelocytes and myeloblasts in the bone marrow) are not eligible

• 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

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Neoplasms
• Neoplasms, Plasma Cell
• Preleukemia
• Syndrome

Intervention

Biological:
• alemtuzumab

Drug:
• cyclosporine

• fludarabine phosphate

• melphalan

• mycophenolate mofetil

Procedure:
• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Moores UCSD Cancer Center	La Jolla	California
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
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	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Engraftment rate		Up to 6 years
Primary	Risk of graft-vs-host disease		Up to 6 years
Primary	Progression-free survival (PFS)		Up to 6 years