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


Phase 2
18 Years
65 Years
Not Enrolling
Both
Lymphoma, Leukemia, Multiple Myeloma, Myelodysplastic Syndrome

Thank you

Trial Information

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


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.


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

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 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).

Outcome Time Frame:

100 days

Safety Issue:

Yes

Principal Investigator

Thomas Spitzer, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital, Harvard University

Authority:

United States: Institutional Review Board

Study ID:

04-222

NCT ID:

NCT00113828

Start Date:

December 2004

Completion Date:

March 2007

Related Keywords:

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

Name

Location
Massachusetts General Hospital Boston, Massachusetts  02114-2617