CD34 Selected Allogeneic Hematopoietic Cell Transplantation With Myeloablative Conditioning and CD8+ Memory T Cell Infusion For Patients With Myelodysplastic Syndrome, Acute Leukemia, and Chronic Myelogenous Leukemia
Overview
- Phase
- Phase 2
- Intervention
- CD8+ Memory T Cell Infusion
- Conditions
- Acute Myeloid Leukemia
- Sponsor
- Robert Lowsky
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- Number of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study will evaluate combining stem cells from the patient's matched sibling donor (a standard CD34-selected transplant) with a second infusion of white blood cells called "CD8 memory T-cells" from their sibling donor.
Detailed Description
Primary Objective: To determine the rate of graft versus host disease (GvHD) free, relapse free survival (GRFS) at one year following CD34 selected allogeneic hematopoietic cell transplantation using myeloablative conditioning combined with an infusion of phenotypic CD8+ memory T cells from human leukocyte antigen (HLA) matched donors for patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML). Secondary Objective: To determine the rate of graft rejection, acute and chronic GvHD, non relapse mortality, relapse, overall survival, and disease free survival.
Investigators
Robert Lowsky
Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Acute leukemia, in morphologic complete remission, OR myelodysplasia with \< 10% blasts in the marrow, and no circulating blasts that contain auer rods. Patients with chronic myelomonocytic leukemia (CMML) must have a WBC count ≤ 10,000 cells/μL and \< 10% blasts in the marrow.
- •Planned myeloablative conditioning regimen at Stanford University Medical Center.
- •Karnofsky or Lansky Performance Score ≥ 70%.
- •Must have an HLA related donor as follows: onor must be an 8/8 match for HLA A, B and C at intermediate (or higher) resolution, and DRB1 at high resolution using DNA based typing. The donors must be willing to receive G CSF followed by collection of cells by apheresis, and must meet the Program's criteria for donation.
- •Cardiac function: Ejection fraction at rest ≥ 40%.
- •Serum creatinine value of \< 1.5 mg/dL, or an estimated creatinine clearance greater than 50 mL/minute (using the Stanford calculator for eGFR available in EPIC)
- •Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50% (adjusted for Hgb)
- •Forced vital capacity (FVC) ≥ 50%.
- •Forced expiratory volume (FEV1) ≥ 50%.
- •Total bilirubin \< 2 times the upper limit of normal (ULN) (unless the elevated bilirubin is attributed to Gilbert's Syndrome)
Exclusion Criteria
- •Prior autologous or allogeneic hematopoietic stem cell transplant
- •Prior malignancies, except resected non melanoma or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously is allowed. Cancer treated with curative intent \< 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs
- •Active central nervous system (CNS) involvement by malignant cells
- •Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
- •Requirement for supplemental oxygen
- •Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
- •History of uncontrolled autoimmune disease or on active treatment (defined as \> 5 mg prednisone daily)
- •Seropositive for HIV 1 or 2
- •Seropositive for HTLV I or -II
- •Active Hepatitis B or C viral replication by polymerase chain reaction (PCR)
Arms & Interventions
fTBI/Thiotepa/fludarabine
Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide.
Intervention: CD8+ Memory T Cell Infusion
fTBI/Thiotepa/fludarabine
Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide.
Intervention: Thiotepa
fTBI/Thiotepa/fludarabine
Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide.
Intervention: Fludarabine
fTBI/Thiotepa/fludarabine
Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide.
Intervention: Hyperfractionated TBI
fTBI/Thiotepa/fludarabine
Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide.
Intervention: Busulfan
fTBI/Thiotepa/fludarabine
Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide.
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Number of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant
Time Frame: 1 year
The rate of participants who do not experience GvHD and also do not experience relapse are collectively considered to be GRFS. Relapse will be assessed according to the myelodysplastic syndrome or leukemia response criteria. The participants will be assessed for GRFS though 1 year post transplant. The outcome will be reported as the number of participants, a number without dispersion.
Secondary Outcomes
- Number of Participants Experiencing Graft Rejection Through 1 Year Post-Transplant(1 year)
- Number of Participants Experiencing Acute Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant(1 year)
- Number of Participants With Chronic, Steroid-Requiring Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant(1 year)
- Number of Participants With Non-Relapse Mortality Through 1 Year Post-Transplant Without Recurrence of Myelodysplastic Syndrome or Leukemia(1 year)
- Number of Participants Who Experience Relapse Through 1 Year Post-Transplant(1 year)
- Overall Survival (OS)(1 year)