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

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.

Study Overview

• Status: Terminated
• Conditions: Lymphoma; Leukemia; Multiple Myeloma; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: MEDI-507; Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant

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
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate progression free and overall survival following HLA mismatched non-myeloablative stem cell transplantation for hematologic malignancy.	36 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Thomas Spitzer, M.D., Massachusetts General Hospital, Harvard University

Study record dates

Study Major Dates

• Study Start: November 1, 2002
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: June 9, 2005
• First Submitted That Met QC Criteria: June 9, 2005
• First Posted (Estimate): June 10, 2005

Study Record Updates

• Last Update Posted (Actual): March 16, 2018
• Last Update Submitted That Met QC Criteria: March 14, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Stem Cell Transplantation; Non-Myeloablative; T-cell Depleted; Mismatched
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Hematologic Neoplasms; Multiple Myeloma
• Other Study ID Numbers: 02-163