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

CD8 Depleted, Non-Engrafting, HLA Mismatched Unrelated Donor Lymphocyte Infusion in Patients With MDA and Secondary AML

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia
• Intervention / Treatment: Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes; Drug: Standard of Care Chemotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: 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; Drug: Standard of Care Chemotherapy; Standard of care cytarabine-based chemotherapy
Experimental: 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	Biological: 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; Drug: Standard of Care Chemotherapy; Standard of care cytarabine-based chemotherapy
Experimental: 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	Biological: 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; Drug: Standard of Care Chemotherapy; Standard of care cytarabine-based chemotherapy
Experimental: 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.	Biological: 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; Drug: Standard of Care Chemotherapy; Standard of care cytarabine-based chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.	Up to 12 months
Progression Free Survival	Progression Free Survival is defined as the time from enrollment to date of progression or death, or censor at last follow-up date.	Up to 12 months
Overall Survival	Overall Survival is defined as the time from study enrollment to death from any cause or censored at last follow up date	Up to 12 months
Hematologic Response	Hematologic response will be determined using International Working Group 2006 criteria for MDS patients and the International Working Group 2003 criteria for AML	Up to 12 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Investigators: Principal Investigator: Joseph Pidala, MD, PhD, Moffitt Cancer Center

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2021
• Primary Completion (Actual): July 20, 2024
• Study Completion (Actual): July 20, 2024

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: MDS; sAML
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes
• Other Study ID Numbers: MCC-20042; G6095 (Other Grant/Funding Number: FDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No