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WithdrawnNCT00085449Updated Nov 27, 2019

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

A Phase 1/2 interventional study of alemtuzumab and cyclosporine in Leukemia, Lymphoma and Multiple Myeloma and Plasma Cell Neoplasm, sponsored by Alliance for Clinical Trials in Oncology. Withdrawn at 24 sites in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2019-11-27.

Sponsored by Alliance for Clinical Trials in Oncology · Phase 1/2, Interventional, and Treatment

Why this study was withdrawn
Funding cut, no patients enrolled
Phase
Phase 1/2
Study type
Interventional
Enrollment
0
Allocation
Not applicable
Ages
18 Years to 60 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

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

Keywords

  • recurrent adult acute myeloid leukemia
  • adult acute myeloid leukemia in remission
  • recurrent adult acute lymphoblastic leukemia
  • adult acute lymphoblastic leukemia in remission
  • myelodysplastic/myeloproliferative neoplasm, unclassifiable
  • previously treated myelodysplastic syndromes
  • atypical chronic myeloid leukemia, BCR-ABL1 negative
  • chronic myelomonocytic leukemia
  • recurrent adult Burkitt lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent small lymphocytic lymphoma
  • recurrent marginal zone lymphoma
  • recurrent mantle cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • accelerated phase chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • refractory chronic lymphocytic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • refractory multiple myeloma
  • secondary myelodysplastic syndromes
  • de novo myelodysplastic syndromes
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

Browse Lymphoma studies →

Lead sponsor

Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    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.

    Biological: alemtuzumab · Drug: cyclosporine · Drug: fludarabine phosphate · Drug: melphalan · Drug: mycophenolate mofetil · Procedure: peripheral blood stem cell transplantation · Radiation: radiation therapy

Interventions

  • Biologicalalemtuzumab
  • Drugcyclosporine
  • Drugfludarabine phosphate
  • Drugmelphalan
  • Drugmycophenolate mofetil
  • Procedureperipheral blood stem cell transplantation
  • Radiationradiation therapy
06

What researchers measure

Primary outcomes

  1. Engraftment rate

    Time frame: Up to 6 years

  2. Risk of graft-vs-host disease

    Time frame: Up to 6 years

  3. Progression-free survival (PFS)

    Time frame: Up to 6 years

07

Study locations

24 sites
  • Moores UCSD Cancer Center
    La Jolla, California 92093-0658, United States
  • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
    Los Angeles, California 90048, United States
  • UCSF Comprehensive Cancer Center
    San Francisco, California 94115, United States
  • CCOP - Christiana Care Health Services
    Newark, Delaware 19713, United States
  • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
    Washington, District of Columbia 20007, United States
  • University of Chicago Cancer Research Center
    Chicago, Illinois 60637-1470, United States
  • Holden Comprehensive Cancer Center at University of Iowa
    Iowa City, Iowa 52242-1009, United States
  • Massachusetts General Hospital Cancer Center
    Boston, Massachusetts 02114, United States
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • University of Minnesota Cancer Center
    Minneapolis, Minnesota 55455, United States
  • Siteman Cancer Center at Barnes-Jewish Hospital
    Saint Louis, Missouri 63110, United States
  • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
    Omaha, Nebraska 68198-7680, United States
  • St. Joseph's Hospital and Medical Center
    Paterson, New Jersey 07503, United States
  • Roswell Park Cancer Institute
    Buffalo, New York 14263-0001, United States
  • Don Monti Comprehensive Cancer Center at North Shore University Hospital
    Manhasset, New York 11030, United States
  • Memorial Sloan-Kettering Cancer Center
    New York, New York 10021, United States
  • Mount Sinai Medical Center
    New York, New York 10029, United States
  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    Chapel Hill, North Carolina 27599-7295, United States
  • Duke Comprehensive Cancer Center
    Durham, North Carolina 27710, United States
  • Wake Forest University Comprehensive Cancer Center
    Winston-Salem, North Carolina 27157-1082, United States
  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
    Columbus, Ohio 43210-1240, United States
  • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
    Pittsburgh, Pennsylvania 15224, United States
  • Hollings Cancer Center at Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Virginia Commonwealth University Massey Cancer Center
    Richmond, Virginia 23298-0037, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 27, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00085449
Lead sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jun 11, 2004
Start date
May 2006
Primary completion
Jan 2007
Completion
Jan 2007
Last update
Nov 27, 2019

Study contacts

Sherif S. Farag, MD, PhD
study chair · Indiana University Melvin and Bren Simon Cancer Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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