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

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT00113828

Collaborator

Dana-Farber Cancer Institute (Other)

Enrollment

Location

Arm

26.9

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Leukemia Multiple Myeloma Myelodysplastic Syndrome	Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant Procedure: T-cell depleted peripheral blood stem cell transplant	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2004

Actual Primary Completion Date :

Mar 1, 2007

Actual Study Completion Date :

Mar 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Transplantation T-cell depleted HLA-matched peripheral blood stem cell transplantation	Procedure: 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. Other Names: Cyclosporine iv beginning on transplant day -1 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 . Other Names: Cyclosporine iv beginning on day -1.

Arm

Intervention/Treatment

Experimental: Transplantation

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

Procedure: 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.

Other Names:

Cyclosporine iv beginning on transplant day -1

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 .

Other Names:

Cyclosporine iv beginning on day -1.

Outcome Measures

Primary Outcome Measures

To evaluate the risks of severe (grade III/IV) GVHD or transplant related mortality at < 100 days following HLA-matched non-myeloablative stem cell transplantation (or following "prophylactic" DLI given for chimerism conversion). [100 days]

Secondary Outcome Measures

To evaluate the incidence of acute and chronic GVHD. [indefinite]
To evaluate the incidence of graft loss. [100 days]
To evaluate progression free and overall survival. [indefinite]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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