Clinical trial NCT04151706: CD34 Selected Allogeneic HCT w/ Myeloablative Conditioning Plus CD8+ Memory TCell Infusion in MDS, AL and CML
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndromes
Acute Leukemia
Chronic Myeloid Leukemia
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2019-11-05
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Recipient 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)
* Alanine aminotransferase (ALT) \< 2.5 x ULN
* Aspartate aminotransferase (AST) \< 2.5 x ULN
* Total bilirubin \< 2 times the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome)
* Signed informed consent

Recipient 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)
* Documented allergy to iron dextran or murine proteins
* Pregnant (positive serum or urine βHCG) or breastfeeding)
* Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use an effective form of birth control or abstinence for one year after transplantation
* Unable to comply with the treatment protocol, including appropriate supportive care, follow up and research tests.
* Planned to receive post transplant maintenance therapy except for fms-like tyrosine kinase 3 (FLT3) inhibitors or BCR ABL tyrosine kinase inhibitors (TKIs).

Donor Inclusion Criteria:

* HLA matched donor (matching at 8/8 antigens or alleles including HLA A, B, C, and -DRB1).
* ≥ 18 years to \< 66.0 years
* State of general good health
* Completed a donor evaluation with history, medical examination and standard blood tests within 60 days of starting the hematopoietic cell collection procedure. In order to fairly represent the interests of the donor, the donor evaluation and consent will be performed by a study team member other than the recipient's attending physician.
* Hepatitis A, B and C, HIV 1 and 2, HTLV, VZV, EBV, HSV, West Nile virus, Syphilis Treponema, T cruzi (Chagas), CMV, and the MPX NAT IDT (HIV/HCV/HBV) will be tested as per national standard of care guidelines for transplant donors. Donors who are HIV positive will be excluded. Donors who are positive by serology for Hepatitis B or C are eligible as long as PCR for RNA/DNA is negative
* White blood cell count \> 3.5 x 109/L
* Platelets \> 150 x 109/L
* Hematocrit \> 35%
* Capable of undergoing leukapheresis
* Able to understand and sign informed consent

Donor Exclusion Criteria:

* Psychological traits or psychological or medical conditions which make them unlikely to tolerate the procedure
* Pregnant or lactating female

Primary outcomes:
measure: Number of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant
timeFrame: 1 year
Secondary outcomes:
measure: Number of Participants Experiencing Graft Rejection Through 1 Year Post-Transplant
timeFrame: 1 year
measure: Number of Participants Experiencing Acute Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant
timeFrame: 1 year
measure: Number of Participants With Chronic, Steroid-Requiring Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant
timeFrame: 1 year
measure: Number of Participants With Non-Relapse Mortality Through 1 Year Post-Transplant Without Recurrence of Myelodysplastic Syndrome or Leukemia
timeFrame: 1 year
measure: Number of Participants Who Experience Relapse Through 1 Year Post-Transplant
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Medical Center
state: California
Study officials:
affiliation: Stanford Medical Center
name: Robert Lowsky, MD
role: PRINCIPAL_INVESTIGATOR
References: