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

This study has suspended participant recruitment.
(Expiration of current lot of MEDI-507, ongoing discussion about future source of MEDI-507)
Sponsor:
Collaborator:
Dana-Farber Cancer Institute
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00113646
First received: June 9, 2005
Last updated: April 1, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Lymphoma
Leukemia
Multiple Myeloma
Myelodysplastic Syndrome
Drug: MEDI-507
Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC 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-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

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. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate progression free and overall survival following HLA mismatched non-myeloablative stem cell transplantation for hematologic malignancy. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: November 2002
Estimated Study Completion Date: December 2007
Estimated Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: MEDI-507
    MEDI-507 0.1 mg/kg on transplant day-8, 0.6 mg/kg on days-7 and -6
    Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant
    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
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.

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113646

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: NCT00113646     History of Changes
Other Study ID Numbers: 02-163
Study First Received: June 9, 2005
Last Updated: April 1, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Non-Myeloablative
T-cell Depleted
Mismatched
Stem Cell Transplantation

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

ClinicalTrials.gov processed this record on July 31, 2014