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

Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Withdrawn
CT.gov ID
NCT00085449
Collaborator
National Cancer Institute (NCI) (NIH)
0
Enrollment
24
Locations
1
Arm
8
Duration (Months)
0
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: alemtuzumab
  • Drug: cyclosporine
  • Drug: fludarabine phosphate
  • Drug: melphalan
  • Drug: mycophenolate mofetil
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: radiation therapy
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Trial of Reduced Intensity Conditioning and Transplantation of Haplotype Mismatched and KIR Class I Epitope-Mismatched Highly Purified CD34 Cells
Study Start Date :
May 1, 2006
Actual Primary Completion Date :
Jan 1, 2007
Actual Study Completion Date :
Jan 1, 2007

Arms and Interventions

ArmIntervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. Engraftment rate [Up to 6 years]

  2. Risk of graft-vs-host disease [Up to 6 years]

  3. Progression-free survival (PFS) [Up to 6 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Moores UCSD Cancer CenterLa JollaCaliforniaUnited States92093-0658
2Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical CenterLos AngelesCaliforniaUnited States90048
3UCSF Comprehensive Cancer CenterSan FranciscoCaliforniaUnited States94115
4CCOP - Christiana Care Health ServicesNewarkDelawareUnited States19713
5Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashingtonDistrict of ColumbiaUnited States20007
6University of Chicago Cancer Research CenterChicagoIllinoisUnited States60637-1470
7Holden Comprehensive Cancer Center at University of IowaIowa CityIowaUnited States52242-1009
8Massachusetts General Hospital Cancer CenterBostonMassachusettsUnited States02114
9Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBostonMassachusettsUnited States02115
10University of Minnesota Cancer CenterMinneapolisMinnesotaUnited States55455
11Siteman Cancer Center at Barnes-Jewish HospitalSaint LouisMissouriUnited States63110
12UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmahaNebraskaUnited States68198-7680
13St. Joseph's Hospital and Medical CenterPatersonNew JerseyUnited States07503
14Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263-0001
15Don Monti Comprehensive Cancer Center at North Shore University HospitalManhassetNew YorkUnited States11030
16Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10021
17Mount Sinai Medical CenterNew YorkNew YorkUnited States10029
18Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel HillNorth CarolinaUnited States27599-7295
19Duke Comprehensive Cancer CenterDurhamNorth CarolinaUnited States27710
20Wake Forest University Comprehensive Cancer CenterWinston-SalemNorth CarolinaUnited States27157-1082
21Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State UniversityColumbusOhioUnited States43210-1240
22Western Pennsylvania Cancer Institute at Western Pennsylvania HospitalPittsburghPennsylvaniaUnited States15224
23Hollings Cancer Center at Medical University of South CarolinaCharlestonSouth CarolinaUnited States29425
24Virginia Commonwealth University Massey Cancer CenterRichmondVirginiaUnited States23298-0037

Sponsors and Collaborators

  • Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)

Investigators

  • Study Chair: Sherif S. Farag, MD, PhD, Indiana University Melvin and Bren Simon Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00085449
Other Study ID Numbers:
  • CALGB-100102
  • CALGB-100102
  • CDR0000370797
First Posted:
Jun 11, 2004
Last Update Posted:
Nov 27, 2019
Last Verified:
Nov 1, 2019
Keywords provided by Alliance for Clinical Trials in Oncology
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 27, 2019