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

NCT ID: NCT04620681

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-14
• Study Completion Date: 2024-07-20

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.

Detailed Description

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).

Patients with advanced MDS are treated with hypomethylating agents (HMAs) such as azacitidine or decitabine. These medications can be effective for a few months to a few years, but usually lose effect eventually. This study is attempting to design a therapy called "non-engrafting, CD8 depleted donor lymphocyte infusion" or "NE-DLI" as a treatment for these diseases.

Conditions

Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Dose Level 1

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

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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

Standard of Care Chemotherapy

Intervention Type: DRUG

Standard of care cytarabine-based chemotherapy

Phase 1 Dose Level 2

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

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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

Standard of Care Chemotherapy

Intervention Type: DRUG

Standard of care cytarabine-based chemotherapy

Phase 1 Dose Level 3

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

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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

Standard of Care Chemotherapy

Intervention Type: DRUG

Standard of care cytarabine-based chemotherapy

Phase 2 -Treatment at Maximum Tolerated Dose (MTD)

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.

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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

Standard of Care Chemotherapy

Intervention Type: DRUG

Standard of care cytarabine-based chemotherapy

Interventions

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

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

Intervention Type: BIOLOGICAL

Standard of Care Chemotherapy

Standard of care cytarabine-based chemotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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
• Left Ventricular Ejection Fraction ≥ 50%
• Willing and able to participate in study assessments

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Pidala, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

G6095

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

MCC-20042

Identifier Type: -

Identifier Source: org_study_id