Clinical trial NCT00113646: Non-Myeloablative HLA-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
Official title: Non-Myeloablative HLA-Mismatched 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
T-cell Depleted
Mismatched
Stem Cell Transplantation
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2005-06-10
Enrollment: 14
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
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.
timeFrame: 36 months
Secondary outcomes:
measure: To evaluate progression free and overall survival following HLA mismatched non-myeloablative stem cell transplantation for hematologic malignancy.
timeFrame: 36 months
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: