CD8 Depleted, Non-engrafting, HLA Mismatched Unrelated Infusion With MDS and Secondary AML

NCT04620681 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MCC-20042G6095
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine the safety of an investigational treatment for myelodysplastic syndrome (MDS) after the first therapy (such as azacitidine or decitabine) stops working or after progression of MDS to acute myeloid leukemia (AML). Funding source - FDA OOPD.

Conditions

Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia

Keywords

MDS; sAML

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of CD8 Depleted Non-engrafting HLA-mismatched Unrelated Donor Lymphocytes Infusion (NE-DLI)

  Maximum Tolerated Dose will be determined by testing increasing doses of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI).

  Up to 60 days per dose level

Secondary Outcomes (4)

• Overall Response Rate

  Up to 12 months

• Progression Free Survival

  Up to 12 months

• Overall Survival

  Up to 12 months

• Hematologic Response

  Up to 12 months

Study Arms (4)

Phase 1 Dose Level 1

EXPERIMENTAL

All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 1: 1X10\^6 CD4 T Cells/kg

Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes; Drug: Standard of Care Chemotherapy

Phase 1 Dose Level 2

EXPERIMENTAL

All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 2: 1X10\^7 CD4 T Cells/kg

Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes; Drug: Standard of Care Chemotherapy

Phase 1 Dose Level 3

EXPERIMENTAL

All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 3: 5 X10\^7 CD4 T Cells/kg

Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes; Drug: Standard of Care Chemotherapy

Phase 2 -Treatment at Maximum Tolerated Dose (MTD)

EXPERIMENTAL

All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at MTD.

Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes; Drug: Standard of Care Chemotherapy

Interventions

Standard of Care Chemotherapy DRUG

Standard of care cytarabine-based chemotherapy

Phase 1 Dose Level 1; Phase 1 Dose Level 2; Phase 1 Dose Level 3; Phase 2 -Treatment at Maximum Tolerated Dose (MTD)

CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes BIOLOGICAL

Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent

Phase 1 Dose Level 1; Phase 1 Dose Level 2; Phase 1 Dose Level 3; Phase 2 -Treatment at Maximum Tolerated Dose (MTD)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Myelodysplastic Syndrome (MDS) having failed hypomethylating agent (HMA) therapy cohort:
• Age 18-79 years, inclusive
• Pathologically confirmed MDS or myelodysplastic/myeloproliferative overlap (MDS/MPN)
• IPSS-R score intermediate, high or very high
• Must have failed therapy with an HMA (defined as lack of response by International Working Group criteria (1) or intolerance of the drug)
• Secondary Acute Myeloid Leukemia (sAML):
• Pathologically confirmed AML according to World Health Organization (WHO) criteria
• Evidence of an antecedent hematologic disorder (AHD) prior to acute leukemia including a known prior diagnosis of MDS, MPN or MDS/MPN or data suggestive of an AHD such as cytopenias, fibrosis, macrocytic anemia, cellular or dysplasia at or prior to the time of diagnosis. If available, MDS-defining karyotypes (-7/del(7q), -5/del(5q), del(13q), del(11q), del(12p), t(12p), del(9q), idic(X)(q13), t(17p) (unbalanced translocations) or i(17q) (ie, loss of 17p), t(11;16)(q23;p13.3), t(3;21)(q26.2;q22.1), t(1;3)(p36.3;q21), t(2;11)(p21;q23), inv(3)(q21q26.2), t(6;9)(p23;q34)) or somatic mutations in multiple genes including p53, TET2, JAK2, CALR, MPL, ASXL1, RUNX1, SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 would also confirm eligibility.
• Age 60-79 years, inclusive
• May be previously untreated
• For both cohorts:
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Deemed eligible to receive cytotoxic chemotherapy
• Creatinine clearance (CrCl)\>50ml/min
• Total bilirubin \<2 mg/dL (except for patients with Gilbert's disease), AST and ALT \< 3x ULN

You may not qualify if:

• Patients who have had systemic chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Hydroxyurea during this period may be given as a bridging therapy to maintain disease stability while awaiting treatment. Intrathecal chemotherapy within this time frame is permitted. Intrathecal chemotherapy may be continued during protocol therapy in order to consolidate or maintain a central nervous system (CNS) remission, but not to treat active CNS disease
• Acute promyelocytic leukemia, or the presence of t(15;17)
• Patients receiving any other investigational agents
• Uncontrolled concurrent illness including, but not limited to, ongoing and uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in the fetus. Breastfeeding should be discontinued if the mother is treated. These potential risks may also apply to other agents used in this study
• Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow-up
• Patients with a poor functional status of ECOG 3-4, or otherwise deemed unfit to tolerate induction chemotherapy.
• Patients with blastic transformation of chronic myelogenous leukemia are ineligible
• Exposure to a humanized mouse chimeric antibody, as this could sensitize patients to components of the CD8 depletion column that may be present in small amounts in the cell product
• Prior allogenic hematopoietic cell transplant

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Joseph Pidala
• Organization: Moffitt Cancer Center

joseph.pidala@moffitt.org

813-745-2556

Study Officials

• Joseph Pidala, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 9, 2020
• Study Start: January 14, 2021
• Primary Completion: July 20, 2024
• Study Completion: July 20, 2024
• Last Updated: February 19, 2026
• Results First Posted: October 22, 2025

Record last verified: 2026-02

Locations

US (1)