CD34 Selected Allogeneic HCT w/ Myeloablative Conditioning Plus CD8+ Memory TCell Infusion in MDS, AL and CML

Robert Lowsky

Status and phase

Completed

Phase 2

Conditions

Acute Leukemia

Chronic Myeloid Leukemia

Acute Lymphoblastic Leukemia

Myelodysplastic Syndromes

Acute Myeloid Leukemia

Treatments

Drug: Cyclophosphamide

Drug: Thiotepa

Drug: Busulfan

Drug: CD8+ Memory T Cell Infusion

Drug: Fludarabine

Radiation: Hyperfractionated TBI

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT04151706

BMT339 (Other Identifier)

IRB-49023 (Other Identifier)

P01CA049605 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

7 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

7 participants in 1 patient group

fTBI/Thiotepa/fludarabine

Experimental group

Description:

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.