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Removal of T Cells to Prevent Graft-Versus-Host Disease in Patients Undergoing Bone Marrow Transplantation

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ClinicalTrials.gov Identifier: NCT00005641
Recruitment Status : Terminated (low study accrual)
First Posted : June 8, 2004
Last Update Posted : December 11, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE May 2, 2000
First Posted Date  ICMJE June 8, 2004
Last Update Posted Date December 11, 2012
Study Start Date  ICMJE September 1997
Actual Primary Completion Date September 2000   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00005641 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Removal of T Cells to Prevent Graft-Versus-Host Disease in Patients Undergoing Bone Marrow Transplantation
Official Title  ICMJE T-Cell Depletion for Graft-Versus-Host Disease (GVHD) Prevention in High Risk Matched and Mismatched Allogeneic Bone Marrow Transplantation
Brief Summary

RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening.

PURPOSE: Phase II trial to study the effectiveness of T cell removal to prevent graft-versus-host disease in patients who are undergoing bone marrow transplantation from a donor.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Myeloproliferative Disorders
  • Graft Versus Host Disease
  • Leukemia
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
Intervention  ICMJE
  • Biological: anti-thymocyte globulin
  • Drug: busulfan
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: leucovorin calcium
  • Drug: methotrexate
  • Drug: methylprednisolone
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: in vitro-treated bone marrow transplantation
  • Radiation: radiation therapy
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE September 2000
Actual Primary Completion Date September 2000   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00005641
Other Study ID Numbers  ICMJE 11587
MCC-11587
MCC-IRB-4599
NCI-G00-1781
BB-IDE-7181 ( Other Identifier: FDA )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Steven C. Goldstein, MD H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP