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

NCT04151706 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-49023BMT339P01CA049605
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant

  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.

  1 year

Secondary Outcomes (6)

• 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

Study Arms (1)

fTBI/Thiotepa/fludarabine

EXPERIMENTAL

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.

Drug: CD8+ Memory T Cell Infusion; Drug: Thiotepa; Drug: Fludarabine; Radiation: Hyperfractionated TBI; Drug: Busulfan; Drug: Cyclophosphamide

Interventions

CD8+ Memory T Cell Infusion DRUG

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

Also known as: Enriched for CD8+CD45RA memory T cells.

fTBI/Thiotepa/fludarabine

Thiotepa DRUG

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

Also known as: Tepadina, thiophosphamide, TESPA

fTBI/Thiotepa/fludarabine

Fludarabine DRUG

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

Also known as: Beneflur

fTBI/Thiotepa/fludarabine

Hyperfractionated TBI RADIATION

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

fTBI/Thiotepa/fludarabine

Busulfan 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

Also known as: Busulfanum

fTBI/Thiotepa/fludarabine

Cyclophosphamide 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

Also known as: Cytoxan, Neosar

fTBI/Thiotepa/fludarabine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Robert Lowsky: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford Medical Center

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Thiotepa; fludarabine; fludarabine phosphate; Busulfan; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated

Results Point of Contact

• Title: Dr. Robert Lowsky
• Organization: Stanford University

rlowsky@stanford.edu

(650) 723-0822

Study Officials

• Robert Lowsky, MD

  Stanford Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 5, 2019
• Study Start: February 27, 2020
• Primary Completion: September 8, 2023
• Study Completion: September 8, 2023
• Last Updated: October 17, 2024
• Results First Posted: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)