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Non-Myeloablative HLA-Mismatched 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
MEDI-507
Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Outcomes
Full info

About this trial

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

Eligibility Criteria

undefined - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Disease Status: NHL, HD, MM that are chemorefractory or relapsed; CLL that is Rai stage III or IV, or lymphocyte doubling time of 6 months, or stage I/II resistant to > 2 cycles of chemotherapy regimens; CML in accelerated or blast phase; MDS with life-threatening cytopenias; patients who have had a previous autologous or allogeneic bone marrow or stem cell transplant; other hematological disorders where allogeneic transplant is appropriate and 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 1 to 3 mismatched (at A, B, DR loci) related donor Exclusion Criteria: Cardiac disease: symptomatic congestive heart failure, ejection fraction of < 45%, active angina pectoris or uncontrolled hypertension. Pulmonary disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or corrected 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 phosphate, SGPT or SGOT > 3 x normal Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation HIV antibody or Hepatitis B surface antigen positivity Uncontrolled infection Presence of HAMA or HAHA in patient previously treated with monoclonal antibody therapy or who have received a product in which the preparation involved a monoclonal antibody affinity step

Sites / Locations

  • Massachusetts General Hospital

Outcomes

Primary Outcome Measures

To evaluate the risk of graft loss and severe GVHD or transplant related mortality at < 100 days following HLA-mismatched non-myeloablative stem cell transplantation.

Secondary Outcome Measures

To evaluate progression free and overall survival following HLA mismatched non-myeloablative stem cell transplantation for hematologic malignancy.

Full Information

First Posted
June 9, 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
NCT00113646
Brief Title
Non-Myeloablative HLA-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
Official Title
Non-Myeloablative HLA-Mismatched 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
Expiration of MEDI-507
Study Start Date
November 2002 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 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

5. Study Description

Brief Summary
The purpose of this study is to determine if recipients of non-myeloablative ex-vivo T-cell depleted peripheral blood (PBSC) stem cell transplantation using a mismatched related donor will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure compared to alternative haploidentical stem cell transplantation.
Detailed Description
One major obstacle to further advancement in the role of bone marrow transplant (BMT) in hematological malignancies is graft-versus-host-disease (GVHD), which can best be prevented by removing T-cells from the donor stem cell product. However, previous experience with T-cell depletion has been associated with an increased rate of engraftment failure and leukemic relapse. Another obstacle is that a large fraction of leukemia and lymphomas afflict older patients who are more prone to GVHD and have co-morbid conditions that prevent them from being a candidate for BMT. This trial uses a non-myeloablative conditioning regimen with cyclophosphamide, MEDI-507, fludarabine, and thymic irradiation followed by a T-cell depleted PBSC infusion. Cyclosporine is used 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, T-cell Depleted, Mismatched, Stem Cell Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
MEDI-507
Intervention Description
MEDI-507 0.1 mg/kg on transplant day-8, 0.6 mg/kg on days-7 and -6
Intervention Type
Procedure
Intervention Name(s)
Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant
Intervention Description
Cyclophosphamide 60 mg/kg on transplant days -7 and -6; Fludarabine 25 mg/m2 days -5,-4,-3,-2,-1; MEDI-507 0.1 mg/kg on day -8, 0.6 mg/kg on days -7,-6
Primary Outcome Measure Information:
Title
To evaluate the risk of graft loss and severe GVHD or transplant related mortality at < 100 days following HLA-mismatched non-myeloablative stem cell transplantation.
Time Frame
36 months
Secondary Outcome Measure Information:
Title
To evaluate progression free and overall survival following HLA mismatched non-myeloablative stem cell transplantation for hematologic malignancy.
Time Frame
36 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Disease Status: NHL, HD, MM that are chemorefractory or relapsed; CLL that is Rai stage III or IV, or lymphocyte doubling time of 6 months, or stage I/II resistant to > 2 cycles of chemotherapy regimens; CML in accelerated or blast phase; MDS with life-threatening cytopenias; patients who have had a previous autologous or allogeneic bone marrow or stem cell transplant; other hematological disorders where allogeneic transplant is appropriate and 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 1 to 3 mismatched (at A, B, DR loci) related donor Exclusion Criteria: Cardiac disease: symptomatic congestive heart failure, ejection fraction of < 45%, active angina pectoris or uncontrolled hypertension. Pulmonary disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or corrected 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 phosphate, SGPT or SGOT > 3 x normal Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation HIV antibody or Hepatitis B surface antigen positivity Uncontrolled infection Presence of HAMA or HAHA in patient previously treated with monoclonal antibody therapy or who have received a product in which the preparation involved a monoclonal antibody affinity step
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
02116
Country
United States

12. IPD Sharing Statement

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

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