A Study to Determine the Safety and Efficacy of Using CD8-High Density Microparticles (CD8-HDM) to Deplete CD8+ Cells From Donor Lymphocyte Infusion in Order to Reduce Graft-versus-Host Disease (GvHD) Without Compromising an Anti-Leukemia Effect in Patients With Chronic Myeloid Leukemia Given HLA-Identical Sibling Peripheral Blood Stem Cell Transplants After Non-Myeloablative Conditioning


Phase 2
50 Years
70 Years
Not Enrolling
Both
Graft Versus Host Disease, Leukemia

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Trial Information

A Study to Determine the Safety and Efficacy of Using CD8-High Density Microparticles (CD8-HDM) to Deplete CD8+ Cells From Donor Lymphocyte Infusion in Order to Reduce Graft-versus-Host Disease (GvHD) Without Compromising an Anti-Leukemia Effect in Patients With Chronic Myeloid Leukemia Given HLA-Identical Sibling Peripheral Blood Stem Cell Transplants After Non-Myeloablative Conditioning


OBJECTIVES: I. Compare the incidence of acute graft versus host disease (GVHD) grades II-IV
and extensive chronic GVHD in chronic myeloid leukemia patients treated with purged donor
lymphocyte infusion (DLI) processed with CD8 high density microparticles (HDM) vs unpurged
DLI following nonmyeloablative, HLA identical sibling peripheral blood stem cell
transplantation. II. Compare the rates of complete cytogenetic, clinical, and hematologic
remission and mortality and GVHD in patients treated with these regimens. III. Determine the
efficacy of CD8 HDM in depleting greater than 95% of CD8+ cells in donor lymphocytes. IV.
Compare the safety and toxicity of these regimens in these patients.

OUTLINE: This is a randomized, double blind, multicenter study. Patients are stratified by
age (under 60 vs 60 and over) and center. Allogeneic peripheral blood stem cells (PBSC) are
harvested and selected for CD34+ cells on days 5-8. Nonmyeloablative conditioning: Patients
receive fludarabine IV over 30 minutes and cytarabine IV over 4 hours (beginning 4 hours
after the start of fludarabine infusion) on days -6 to -3 and idarubicin IV over 1-5 minutes
on days -6 to -4. Filgrastim (G-CSF) is administered subcutaneously daily beginning on day
-2 and continues until blood counts recover. Graft versus host disease prevention: Beginning
on day -2, patients receive tacrolimus IV continuously until oral dosing is tolerated.
Patients receive tacrolimus in combination with methotrexate on days 1, 3, and 6 after
completion of transplantation. Beginning 12 weeks after completion of transplantation, oral
tacrolimus is tapered and stopped over 4 weeks. Transplantation: Allogeneic PBSC are infused
on day 0. At 4 months posttransplantation, patients with residual Ph+ cells by cytogenetics
or FISH OR hematologic or clinical evidence of chronic myeloid leukemia AND without
symptomatic chronic graft versus host disease requiring immunosuppressive therapy are
randomized to 1 of 2 treatment arms: Arm I: Lymphocytes harvested from the original PBSC
donor are processed with the CD8 high density microparticle device to remove all or most
CD8+ cells. Patients receive CD8+ cell depleted donor lymphocyte infusion (DLI) IV over
15-30 minutes on the same day of collection. Arm II: Lymphocytes are harvested from the
original PBSC donor. Patients receive undepleted DLI IV over 15-30 minutes on the same day
of collection. Patients are followed at days 30, 60, 100, and 180, and then periodically
through year 5.

PROJECTED ACCRUAL: A maximum of 110 patients (55 per arm) will be accrued for this study
within 1 year.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically proven chronic myeloid leukemia (CML) in first
chronic phase or with cytogenetic but not hematologic evidence of acceleration (clonal
evolution) Availability of 6 antigen (A, B, and DR loci) HLA identical sibling donor
Eligible for randomization to donor lymphocyte infusion (DLI) if: Residual Ph+ cells by
cytogenetics or FISH or hematologic or clinical evidence of CML AND No graft versus host
disease requiring immunosuppressive therapy within the past 2 weeks AND Evidence of donor
hematopoiesis after completion of transplantation Ineligible for randomization to DLI if:
Blast transformation of CML OR Prior interferon alfa for relapse after completion of
transplantation

PATIENT CHARACTERISTICS: Age: 50 to 70 Performance status: Zubrod 0-2 Life expectancy: Not
specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 3 mg/dL
Renal: Creatinine less than 2 mg/dL Cardiovascular: Cardiac ejection fraction greater than
40% Pulmonary: DLCO greater than 45% predicted Other: No active infection Not pregnant
Negative pregnancy test No hypersensitivity to nickel No hypersensitivity to mouse
proteins Human antimouse antibody positivity allowed if no allergic history HIV negative
HTLV antibody negative

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent
hematopoietic growth factors other than filgrastim (G-CSF) No other biologic therapy
(e.g., interferon alfa) for 6 months after completion of study therapy Chemotherapy: No
other chemotherapy for 6 months after completion of study therapy Concurrent hydroxyurea
allowed for CML relapse Endocrine therapy: Concurrent methylprednisolone allowed if grade
II or worse GVHD develops Radiotherapy: No radiotherapy for 6 months after completion of
study therapy Surgery: Not specified

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Supportive Care

Principal Investigator

Gary J. Schiller, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000067538

NCT ID:

NCT00004878

Start Date:

Completion Date:

Related Keywords:

  • Graft Versus Host Disease
  • Leukemia
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • Philadelphia chromosome positive chronic myelogenous leukemia
  • graft versus host disease
  • Graft vs Host Disease
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive

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