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

Primary Purpose

Lymphoma, Leukemia, Multiple Myeloma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant
T-cell depleted peripheral blood stem cell transplant
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring Non-Myeloablative, Stem Cell Transplantation, T-cell Depletion, HLA-Matched

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transplantation

Arm Description

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

Outcomes

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).

Secondary Outcome Measures

To evaluate the incidence of acute and chronic GVHD.
To evaluate the incidence of graft loss.
To evaluate progression free and overall survival.

Full Information

First Posted
June 10, 2005
Last Updated
March 14, 2018
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00113828
Brief Title
Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
Official Title
Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Terminated
Why Stopped
Insufficient accrual
Study Start Date
December 2004 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
March 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Leukemia, Multiple Myeloma, Myelodysplastic Syndrome
Keywords
Non-Myeloablative, Stem Cell Transplantation, T-cell Depletion, HLA-Matched

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Transplantation
Arm Type
Experimental
Arm Description
T-cell depleted HLA-matched peripheral blood stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant
Other Intervention Name(s)
Cyclosporine iv beginning on transplant day -1
Intervention Description
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
Intervention Name(s)
T-cell depleted peripheral blood stem cell transplant
Other Intervention Name(s)
Cyclosporine iv beginning on day -1.
Intervention Description
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 .
Primary Outcome Measure Information:
Title
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).
Time Frame
100 days
Secondary Outcome Measure Information:
Title
To evaluate the incidence of acute and chronic GVHD.
Time Frame
indefinite
Title
To evaluate the incidence of graft loss.
Time Frame
100 days
Title
To evaluate progression free and overall survival.
Time Frame
indefinite

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Spitzer, M.D.
Organizational Affiliation
Massachusetts General Hospital, Harvard University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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