Clinical trial NCT00113828: Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
Official title: Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoma
Leukemia
Multiple Myeloma
Myelodysplastic Syndrome
Keywords: Non-Myeloablative
Stem Cell Transplantation
T-cell Depletion
HLA-Matched
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2005-06-13
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to determine if patients with hematologic diseases who have a HLA 6/6 matched related donor and are not eligible for a standard myeloablative stem cell transplant will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure when treated with a non-myeloablative T-cell depleted stem cell transplant.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
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).
timeFrame: 100 days
Secondary outcomes:
measure: To evaluate the incidence of acute and chronic GVHD.
timeFrame: indefinite
measure: To evaluate the incidence of graft loss.
timeFrame: 100 days
measure: To evaluate progression free and overall survival.
timeFrame: indefinite
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital, Harvard University
name: Thomas Spitzer, M.D.
role: PRINCIPAL_INVESTIGATOR
References: