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

NCT ID: NCT04151706

Last Updated: 2024-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-27
• Study Completion Date: 2023-09-08

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.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Acute Leukemia; Chronic Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CD8+ Memory T Cell Infusion

Intervention Type: DRUG

Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation

Thiotepa

Intervention Type: DRUG

5 mg/kg/day: IV for 2 consecutive days (days -6 to -5)

Fludarabine

Intervention Type: DRUG

25 mg/m2/day: IV for 5 consecutive days (days -6 to -2)

Hyperfractionated TBI

Intervention Type: RADIATION

Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy)

Busulfan

Intervention Type: DRUG

6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg

Cyclophosphamide

Intervention Type: DRUG

60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg

Interventions

CD8+ Memory T Cell Infusion

Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation

Intervention Type: DRUG

Thiotepa

5 mg/kg/day: IV for 2 consecutive days (days -6 to -5)

Intervention Type: DRUG

Fludarabine

25 mg/m2/day: IV for 5 consecutive days (days -6 to -2)

Intervention Type: DRUG

Hyperfractionated TBI

Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy)

Intervention Type: RADIATION

Busulfan

6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg

Intervention Type: DRUG

Cyclophosphamide

60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg

Intervention Type: DRUG

Other Intervention Names

Enriched for CD8+CD45RA memory T cells.; Tepadina; thiophosphamide; TESPA; Beneflur; Busulfanum; Cytoxan; Neosar

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)
• 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

• 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

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).

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Robert Lowsky

OTHER

Sponsor Role: lead

Responsible Party

Robert Lowsky

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robert Lowsky, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford Medical Center

Locations

Stanford Medical Center

Stanford, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

BMT339

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-49023

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA049605

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-49023

Identifier Type: -

Identifier Source: org_study_id