Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies

NCT ID: NCT00113828

Last Updated: 2018-03-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2007-03-31

Brief Summary

The purpose of this trial is to determine if patients with hematologic diseases who have a HLA 6/6 matched related donor and are not eligible for a standard myeloablative stem cell transplant will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure when treated with a non-myeloablative T-cell depleted stem cell transplant.

Detailed Description

Our prior experience in the lab and in clinical trials with non-myeloablative HLA-matched and mismatched transplant strategies have been remarkable for a low transplant related mortality rate, but a still formidable risk of GVHD and graft rejection. In this trial, we have incorporated a combination ex-vivo T-cell depletion strategy to prevent GVHD with vigorous in vivo depletion of host (and to a lesser extent donor) T-cells to prevent graft rejection.

Patients will receive non-myeloablative conditioning with cyclophosphamide, thymoglobulin, fludarabine, and thymic irradiation, followed by a T-cell depleted PBSC infusion. Cyclosporine will be given for GVHD prophylaxis, and tapered beginning on day 35. Data from our mouse model and previous clinical trials have demonstrated that this approach can induce mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full donor hematopoiesis following donor leukocyte infusions.

Conditions

Lymphoma; Leukemia; Multiple Myeloma; Myelodysplastic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Transplantation

T-cell depleted HLA-matched peripheral blood stem cell transplantation

Group Type: EXPERIMENTAL

Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant

Intervention Type: PROCEDURE

Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7 and 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days-7,-6; fludarabine 25 mg/m2 on days -5, -4, -3, -2, -1.

Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant.

T-cell depleted peripheral blood stem cell transplant

Intervention Type: PROCEDURE

Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7, 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days -7, -6; fludarabine 25 mg/m2 on days -5 through -1.

T-cell depleted peripheral blood stem cell transplant .

Interventions

Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant

Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7 and 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days-7,-6; fludarabine 25 mg/m2 on days -5, -4, -3, -2, -1.

Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant.

Intervention Type: PROCEDURE

T-cell depleted peripheral blood stem cell transplant

Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7, 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days -7, -6; fludarabine 25 mg/m2 on days -5 through -1.

T-cell depleted peripheral blood stem cell transplant .

Intervention Type: PROCEDURE

Other Intervention Names

Cyclosporine iv beginning on transplant day -1; Cyclosporine iv beginning on day -1.

Eligibility Criteria

Inclusion Criteria

• Disease statue: NHL, HD, or MM that are chemorefractory or relapsed; CLL that is Rai Stage III/IV, or lymphocyte doubling time of 6 months, or stage I/II that is resistant to > 2 chemotherapy regimens; AML or ALL in 1st or subsequent remission with poor prognostic features; CML in accelerated or blast phae; MDS with life-threatening cytopenias; patients who have had a previous autologous or allogeneic bone marrow or stem cell transplant; other hematologic disorders which allogeneic stem cell transplantation is appropriate where the risk of conventional transplantation is considered to be unacceptably high.
• Estimated disease-free survival of less than one year
• ECOG performance status of 0, 1, or 2
• HLA-genotypically or phenotypically matched (at A, B, DR loci) related donor

Exclusion Criteria

• Patients who life expectancy is limited by diseases other than their hematologic malignancy.
• Cardiac Disease: symptomatic congestive hearth failure, or RVG, or ejection fraction of < 45%, active angina pectoris, or uncontrolled hypertension.
• Pulmonary Disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or DLCO of < 50%.
• Renal Disease: serum creatinine > 2.0 mg/dl or creatinine clearance < 50 ml/min.
• Hepatic Disease: serum bilirubin > 2.0 mg/dl or alkaline phosphatase, SGOT or SGPT > 3 times normal.
• Neurologic Disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation
• HIV or HTLV I antibody or Hepatitis B surface antigen positivity
• Uncontrolled infection

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Thomas Spitzer

Director, Bone Marrow Transplant Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Spitzer, M.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital, Harvard University

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

04-222

Identifier Type: -

Identifier Source: org_study_id