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


Phase 2
N/A
65 Years
Not Enrolling
Both
Lymphoma, Leukemia, Multiple Myeloma, Myelodysplastic Syndrome

Thank you

Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

36 months

Safety Issue:

Yes

Principal Investigator

Thomas Spitzer, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital, Harvard University

Authority:

United States: Food and Drug Administration

Study ID:

02-163

NCT ID:

NCT00113646

Start Date:

November 2002

Completion Date:

December 2007

Related Keywords:

  • Lymphoma
  • Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndrome
  • Non-Myeloablative
  • T-cell Depleted
  • Mismatched
  • Stem Cell Transplantation
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms

Name

Location
Massachusetts General Hospital Boston, Massachusetts  02114-2617