Non-Myeloablative HLA-Matched Ex-Vivo T-Cell Depleted Stem Cell Transplantation for Hematologic Malignancies - Full Text View

Purpose

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	Intervention	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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Non-Myeloablative HLA-Matched Ex-Vivo T-Cell Depleted Stem Cell Transplantation for Hematologic Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes

Drug Information available for: Cyclosporine

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

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). [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate the incidence of acute and chronic GVHD. [ Time Frame: indefinite ] [ Designated as safety issue: Yes ]
To evaluate the incidence of graft loss. [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
To evaluate progression free and overall survival. [ Time Frame: indefinite ] [ Designated as safety issue: Yes ]

Enrollment:	5
Study Start Date:	December 2004
Study Completion Date:	March 2007
Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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. Other Name: 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. Other Name: Cyclosporine iv beginning on day -1.

Arms

Assigned Interventions

Experimental: 1

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.

Other Name: 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.

Other Name: Cyclosporine iv beginning on day -1.

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113828

Locations

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02116

Sponsors and Collaborators

Massachusetts General Hospital

Dana-Farber Cancer Institute

Investigators

Principal Investigator:

Thomas Spitzer, M.D.

Massachusetts General Hospital, Harvard University

More Information

No publications provided

Responsible Party:	Thomas Spitzer, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00113828 History of Changes
Other Study ID Numbers:	04-222
Study First Received:	June 10, 2005
Last Updated:	December 28, 2007
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:

Non-Myeloablative
Stem Cell Transplantation
T-cell Depletion
HLA-Matched

Additional relevant MeSH terms:

Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases

Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Neoplasms by Site
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on May 23, 2013