Clinical trial NCT00968864: T-cell Depleted Alternative Donor Transplantation
Official title: A Phase II Study Using the CliniMACS® Device for CD34+ Cell Selection and T Cell Depletion for Graft-versus-Host Disease Prophylaxis in Alternative Donor Stem Cell Transplant Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Chronic Myeloid Leukemia
Myelodysplastic Syndrome
Lymphomas
Bone Marrow Failure
Hemoglobinopathy
Immune Deficiency
Osteopetrosis
Keywords: T cell depleted
Matched unrelated donors
Haplocompatible donors
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2009-08-31
Enrollment: 53
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose is to determine the ability of CD34+ selection and T cell depletion using the CliniMACS® device to prevent severe acute graft-versus-host disease (GVHD) in patients receiving a stem cell transplant from an alternative (unrelated and mismatched related) donor. The secondary objectives include evaluation of engraftment, immune recovery, and post-transplant infections.

Patients requiring stem cell transplants for either malignant (cancerous) or non-malignant disease will be included in the study. The recipients will be grouped into one of two groups based on whether the donor is mismatched related (Cohort A) or unrelated (Cohort B). The patient will receive a conditioning regimen including chemotherapy drugs and/or total body irradiation based on the disease for which the transplant is performed.

Detailed description: A major issue in alternative donor (mismatched related and unrelated donor transplantation is the development of graft-versus-host disease (GVHD). Several clinical trials have shown that the use of T-cell depleted peripheral blood stem cells (PBSC) reduces GVHD in alternative donor transplants. The purpose of this study is to determine the ability of CD34 positive selection and T cell depletion using the CliniMACS® Device as the only GVHD prophylaxis to prevent severe acute GVHD in recipients of an alternative donor PBSC transplant. Mismatched related donors will match at least 3 of 6 Human leukocyte antigens(HLA)(haplocompatible) and unrelated donors will match at least 6 out of 8 HLA antigens with the transplant recipient. The conditioning therapy including chemotherapy, anti-thymocyte globulin (ATG), +/- total body irradiation (TBI) will be based on the patient's diagnosis. The transplant recipient will be followed for 5 years after transplant for GVHD, engraftment, post-transplant infections, disease relapse, and overall survival. In addition, this study will serve as a platform for a companion study of therapy to accelerate immune recovery after transplant.

Eligibility criteria: Inclusion Criteria:

* Age \< 30 years
* Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias, white and red blood cell abnormalities, and immunodeficiencies.
* Patients with acute lymphoblastic leukemia must be in morphological remission (\< 5% blasts) at the time of transplant. Patients with acute non-lymphocytic leukemia will preferably be in morphologic remission but may be enrolled when aplastic after chemotherapy or with \< 20% blasts. Patients with lymphoma must be in complete or close to complete remission (if residual adenopathy, PET scan must be negative or only have slight uptake, eg. SUV \< 2).
* Patients must lack a healthy HLA-identical related donor of at least one year of age.
* Patient must have a mismatched related or an unrelated donor who is:

  1. Able to receive G-CSF and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter,
  2. Healthy,
  3. Willing,
  4. For recipients of an unrelated donor transplant, recipient eligibility will be restricted as follows if in the judgment of the recipients' transplant physician, the recipient cannot receive a transplant with combined positive and negative fractions as described in Section 6.1.3.2 or an unmanipulated PBSC product.
  5. Meets eligibility criteria for donors.
* If only one mismatched related relative is available, an acceptable unrelated donor must be identified as a backup.
* Patient or authorized guardian must sign informed consent for this study.

Exclusion Criteria:

* Patient with an anticipated life expectancy of \< 1 month
* Active infectious hepatitis or CMV infection
* HIV or HTLV-I/II infection
* Serious infection (bacterial, fungal, viral) within the last 4 weeks
* Cardiac ejection fraction \< 45%; can be lower if patient is not in clinical cardiac failure and a reduced intensity conditioning regimen is used.
* Creatinine clearance \<60 ml/min/1.72 m2; can be lower if a reduced intensity conditioning regimen is used.
* Pulmonary diffusion capacity (adjusted for Hgb), FEV1, or FVC \<60% of predicted or O2 sat \< 94% if unable to perform PFTs; can be lower if a reduced intensity conditioning regimen is used.
* Serum ALT \> 3 x upper limit of normal (can be up to 5 x upper limit of normal if a reduced intensity conditioning regimen is used) or bilirubin \> 2. The bilirubin criteria for sickle cell disease patients is direct bilirubin \>2x upper limit of normal.
* Performance score (Lansky/Karnofsky) \< 50
* Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.

Primary outcomes:
measure: Number of Participants With Severe Graft vs. Host Disease (GVHD).
timeFrame: Within 30 days after stem cell transplant
Secondary outcomes:
measure: Number of Participants With Engraftment and Time to Engraftment
timeFrame: Within 28 days after stem cell transplant
measure: Number of Participants With Post-transplant Infections
timeFrame: 1 year
measure: Number of Participants With EBV-related Post Transplant Lymphoproliferative Disorder (PTLD)
timeFrame: 5 years
measure: Number of Participants With Post-transplant Leukemia Relapse
timeFrame: 5 years
measure: Number of Participants With Transplant-related Mortality
timeFrame: 2 year
measure: Number of Participants With Transplant-related Toxicities
timeFrame: 1 year
measure: Overall Survival
timeFrame: 2 years
measure: Device Performance: Dose of CD34+ Cells and CD3+ Cells Given
timeFrame: Length of the trial (5 years)
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Levine Children's Hospital, Carolinas Medical Center
state: North Carolina
Study officials:
affiliation: Department of Pediatrics, Levine Children's Hospital, Carolinas Healthcare System
name: Andrew Gilman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gilman AL, Eckrich MJ, Epstein S, Barnhart C, Cannon M, Fukes T, Hyland M, Shah K, Grochowski D, Champion E, Ivanova A. Alternative donor hematopoietic stem cell transplantation for sickle cell disease. Blood Adv. 2017 Jun 28;1(16):1215-1223. doi: 10.1182/bloodadvances.2017005462. eCollection 2017 Jul 11.