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

December 10, 2012 updated by: H. Lee Moffitt Cancer Center and Research Institute

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Steven C. Goldstein, MD, H. Lee Moffitt Cancer Center and Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1997

Primary Completion (Actual)

September 1, 2000

Study Completion (Actual)

September 1, 2000

Study Registration Dates

First Submitted

May 2, 2000

First Submitted That Met QC Criteria

June 7, 2004

First Posted (Estimate)

June 8, 2004

Study Record Updates

Last Update Posted (Estimate)

December 11, 2012

Last Update Submitted That Met QC Criteria

December 10, 2012

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11587
  • MCC-11587
  • MCC-IRB-4599
  • NCI-G00-1781
  • BB-IDE-7181 (Other Identifier: FDA)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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