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T-Cell Depletion for Graft-Versus-Host Disease (GVHD) Prevention in High Risk Matched and Mismatched Allogeneic Bone Marrow Transplantation

Phase 2
15 Years
60 Years
Not Enrolling
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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Trial Information

T-Cell Depletion for Graft-Versus-Host Disease (GVHD) Prevention in High Risk Matched and Mismatched Allogeneic Bone Marrow Transplantation

OBJECTIVES: I. Determine the incidence and severity of graft vs host disease (GVHD)
following allogeneic bone marrow transplantation with marrow grafts modified by T cell
depletion with counterflow centrifugal elutriation and CD34+ cell selection in patients at
high risk for GVHD. II. Determine the incidence of graft failure following this treatment
regimen in this patient population. III. Determine the relapse rate and overall survival in
this patient population treated with this regimen.

OUTLINE: Patients with unrelated donors, mismatched related donors, or matched related
donors diagnosed with acute lymphocytic leukemia, chronic lymphocytic leukemia, myeloma, or
advanced acute myeloid leukemia (AML), receive cyclophosphamide IV over 60 minutes on days
-6 and -5 and fractionated total body irradiation (TBI) 3 times a day on days -3 through -1,
and twice on day 0. Patients receive graft vs host disease (GVHD) prophylaxis with
anti-thymocyte globulin (ATG) IV over 8 hours on days -2 and -1. Patients undergo allogeneic
bone marrow transplantation (ABMT) on day 0 with marrow grafts modified by T cell depletion
with counterflow centrifugal elutriation and CD34+ selection. Patients unable to receive TBI
due to matched or mismatched related donors, or age (56 to 60), or patients diagnosed with
AML-CR1, chronic myelogenous leukemia, myelodysplastic syndrome, or myeloproliferative
disorders with matched related donors, receive oral busulfan every 6 hours on days -7
through -4, cyclophosphamide IV over 60 minutes on days -3 and -2, and ATG IV over 8 hours
on days -2 and -1 for GVHD prophylaxis. Patients undergo T cell depleted ABMT on day 0. At
pretransplantation, patients with acute leukemia receive intrathecal (IT) methotrexate (MTX)
following lumbar puncture. At 48 hours following IT MTX, patients with CNS involvement
receive a second dose of IT MTX followed by oral leucovorin calcium every 6 hours for 4
doses. Patients with prior CNS involvement receive cranial radiotherapy for 2 weeks.
Following AMBT, patients undergo GVHD prophylaxis consisting of methylprednisolone IV every
12 hours on days 5-22, and then once daily on days 23-28 and cyclosporine IV or orally twice
daily beginning on day -1 and continuing until 7-9 months following ABMT. Patients are
followed every 3 months until death.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed malignancy Acute myeloid leukemia (AML)
Complete remission 1 (CR1): high risk defined by poor cytogenetics (e.g., deletions,
additions, or multiple abnormalities) Complete remission 2 (CR2) Induction failures
Relapse: at least one reinduction attempt if at least 10% marrow blasts Acute lymphocytic
leukemia CR1: high risk defined by overt CNS involvement or poor cytogenetics (e.g.,
additions, deletions, translocations, or multiple abnormalities) CR2 Induction failures
Relapse as for AML Chronic myelogenous leukemia Chronic phase (CP) 1 Accelerated phase
(AP)/CP2: blast phase patients require induction and achievement of a second chronic phase
prior to transplantation Chronic lymphocytic leukemia Relapse: any stage and must have
received no greater than 3 regimens since diagnosis Multiple myeloma Primary refractory
disease at diagnosis Relapse (no greater than 2): sensitive disease Plasma cell leukemia
Inability to achieve a complete remission or relapse after autologous transplantation (no
greater than 40 years) Myelodysplasia All FAB subtypes Myeloproliferative disorders Poor
response to medical therapy OR Cytogenetic abnormalities Severe aplastic anemia (SAA) (for
unrelated and/or mismatched donors) Very SAA at diagnosis OR SAA: induction failures One
antigen mismatch (recipient age 15 to 55) Related donors may be A, B, or DR mismatched
Unrelated donors may be A or B mismatched (DRB1 match) Phenotypic (6 out of 6) match
Recipient age 51 to 60 if related donor Recipient age 41 to 55 if unrelated donor

PATIENT CHARACTERISTICS: Age: 15 to 60 Performance status: ECOG 0-1 Life expectancy: Not
specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL
SGOT/SGPT no greater than 3 times normal PT/PTT normal Renal: Creatinine no greater than
2.0 mg/dL Creatinine clearance at least 60 mL/min Cardiovascular: LVEF at least 45% by
MUGA scan or echocardiography Greater than 6 months since myocardial infarction No
uncontrolled arrhythmias Pulmonary: FEV1 and DCLO at least 50% predicted Other: No
psychosocial conditions that would preclude study No uncontrolled diabetes mellitus No
uncontrolled thyroid disease No active serious infections HIV negative Not pregnant or
nursing Negative pregnancy test

PRIOR CONCURRENT THERAPY: See Disease Characteristics

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Steven C. Goldstein, MD

Investigator Role:

Study Chair

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

September 1997

Completion Date:

September 2000

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Graft Versus Host Disease
  • Leukemia
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • recurrent childhood acute lymphoblastic leukemia
  • refractory multiple myeloma
  • stage 0 chronic lymphocytic leukemia
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • stage I chronic lymphocytic leukemia
  • stage II chronic lymphocytic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • recurrent childhood acute myeloid leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • relapsing chronic myelogenous leukemia
  • refractory chronic lymphocytic leukemia
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • adult acute myeloid leukemia in remission
  • adult acute lymphoblastic leukemia in remission
  • polycythemia vera
  • primary myelofibrosis
  • essential thrombocythemia
  • refractory anemia
  • refractory anemia with ringed sideroblasts
  • refractory anemia with excess blasts
  • refractory anemia with excess blasts in transformation
  • chronic myelomonocytic leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • graft versus host disease
  • refractory cytopenia with multilineage dysplasia
  • childhood myelodysplastic syndromes
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612