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

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ClinicalTrials.gov Identifier: NCT00113646
Recruitment Status : Terminated (Expiration of MEDI-507)
First Posted : June 10, 2005
Last Update Posted : March 16, 2018
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Thomas Spitzer, Massachusetts General Hospital

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.

Condition or disease Intervention/treatment Phase
Lymphoma Leukemia Multiple Myeloma Myelodysplastic Syndrome Drug: MEDI-507 Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Non-Myeloablative HLA-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
Study Start Date : November 2002
Primary Completion Date : December 2007
Study Completion Date : December 2007

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

Primary Outcome Measures :
  1. 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 Measures :
  1. To evaluate progression free and overall survival following HLA mismatched non-myeloablative stem cell transplantation for hematologic malignancy. [ Time Frame: 36 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00113646

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02116
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Principal Investigator: Thomas Spitzer, M.D. Massachusetts General Hospital, Harvard University

Responsible Party: Thomas Spitzer, Director Cellular Therapy and Transplantation Laboratory, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00113646     History of Changes
Other Study ID Numbers: 02-163
First Posted: June 10, 2005    Key Record Dates
Last Update Posted: March 16, 2018
Last Verified: March 2018

Keywords provided by Thomas Spitzer, Massachusetts General Hospital:
T-cell Depleted
Stem Cell Transplantation

Additional relevant MeSH terms:
Multiple Myeloma
Myelodysplastic Syndromes
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions