CompletedNCT04620681Updated Feb 19, 2026Results posted

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

A Phase 1/2 interventional study of CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes and Standard of Care Chemotherapy in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia, sponsored by H. Lee Moffitt Cancer Center and Research Institute. Completed at 1 site in United States. Open to participants aged 18 Years to 79 Years. Per ClinicalTrials.gov, last updated 2026-02-19.

Sponsored by H. Lee Moffitt Cancer Center and Research Institute · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 19
Allocation: Non-randomized
Ages: 18 Years to 79 Years
Sex: All

Study 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.

Read the detailed description

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 studied

Myelodysplastic Syndromes
Secondary Acute Myeloid Leukemia

Browse trials for

Myelodysplastic Syndromes 2,124

Keywords

MDS
sAML

In context

Myelodysplastic Syndromes

2,124 studies on the registry are indexed under Myelodysplastic Syndromes; 320 are open to participants now.

This study's enrollment of 19 is below the median of 39 across 1,740 interventional studies indexed under Myelodysplastic Syndromes.

Browse Myelodysplastic Syndromes studies →

Lead sponsor

H. Lee Moffitt Cancer Center and Research Institute is the lead sponsor of 533 studies on the registry; 74 are open to participants now.

Of its 99 completed or terminated interventional studies of FDA-regulated products, 57 (58%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 79 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 19 participants (actual)

Study arms

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 · Drug: Standard of Care 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 · Drug: Standard of Care 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 · Drug: Standard of Care 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 · Drug: Standard of Care Chemotherapy

Interventions

BiologicalCD8 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
DrugStandard of Care Chemotherapy
Standard of care cytarabine-based chemotherapy

What researchers measure

Primary outcomes

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).
Time frame: Up to 60 days per dose level

Secondary outcomes

Overall Response Rate
Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: Up to 12 months

Results

Posted Oct 22, 2025

Participant flow

Participant flow — Overall Study
Milestone	Phase 1 Dose Level 1	Phase 1 Dose Level 2	Phase 1 Dose Level 3	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)
Started	3	3	3	10
Completed	3	3	3	10
Not completed	0	0	0	0

Outcome measures

PrimaryMaximum 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).

Time frame:: Up to 60 days per dose level
Reported as:: Number · 10^7 CD4 cells/kg

Maximum Tolerated Dose of CD8 Depleted Non-engrafting HLA-mismatched Unrelated Donor Lymphocytes Infusion (NE-DLI)
10^7 CD4 cells/kg	Maximum Tolerated Dose (MTD)
Maximum Tolerated Dose of CD8 Depleted Non-engrafting HLA-mismatched Unrelated Donor Lymphocytes Infusion (NE-DLI)	5

SecondaryOverall Response Rate

Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.

Time frame:: Up to 12 months
Reported as:: Number · percentage of Participants with Response

Overall Response Rate
percentage of Participants with Response	Participants Treated at MTD
Overall Response Rate	61.5 (31.6 to 86.1)

SecondaryProgression 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.

Time frame:: Up to 12 months
Reported as:: Median · Months

Progression Free Survival
Months	Participants Treated at MTD
Progression Free Survival	8.7 (1.4 to NA)

SecondaryOverall Survival

Overall Survival is defined as the time from study enrollment to death from any cause or censored at last follow up date

Time frame:: Up to 12 months
Reported as:: Median · Months

Overall Survival
Months	Participants Treated at MTD
Overall Survival	11.9 (2.5 to NA)

SecondaryHematologic Response

Hematologic response will be determined using International Working Group 2006 criteria for MDS patients and the International Working Group 2003 criteria for AML

Time frame:: Up to 12 months
Reported as:: Number · Number of Participants achieving CR

Hematologic Response
Number of Participants achieving CR	Participants Treated at MTD - sAML	Participants Treated at MTD - MDS
Hematologic Response	7	0

Adverse events

Collected over 1 Year. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase 1 Dose Level 1	3/3 (100%)	2/3 (66.7%)	3/3 (100%)
Phase 1 Dose Level 2	3/3 (100%)	0/3 (0%)	3/3 (100%)
Phase 1 Dose Level 3	2/3 (66.7%)	3/3 (100%)	3/3 (100%)
Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	5/10 (50%)	1/10 (10%)	10/10 (100%)

Most frequent serious events

Most frequent serious events
Event	Phase 1 Dose Level 1	Phase 1 Dose Level 2	Phase 1 Dose Level 3	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)
FeverGeneral disorders	1/3	0/3	0/3	0/10
Lung InfectionInfections and infestations	0/3	0/3	1/3	0/10
SepsisInfections and infestations	1/3	0/3	0/3	1/10
Skin InfectionInfections and infestations	0/3	0/3	1/3	0/10
DeliriumPsychiatric disorders	0/3	0/3	1/3	0/10
HypoxiaRespiratory, thoracic and mediastinal disorders	1/3	0/3	0/3	0/10
PneumonitisRespiratory, thoracic and mediastinal disorders	1/3	0/3	0/3	0/10

Most frequent other events

Showing 10 of 25

Most frequent other events
Event	Phase 1 Dose Level 1	Phase 1 Dose Level 2	Phase 1 Dose Level 3	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)
SepsisInfections and infestations	2/3	3/3	2/3	4/10
White blood cell decreasedInvestigations	3/3	0/3	0/3	1/10
Lung infectionInfections and infestations	0/3	0/3	2/3	1/10
Platelet count decreasedInvestigations	2/3	1/3	1/3	2/10
HypoxiaRespiratory, thoracic and mediastinal disorders	2/3	0/3	0/3	0/10
AnemiaBlood and lymphatic system disorders	1/3	0/3	0/3	0/10
Febrile neutropeniaBlood and lymphatic system disorders	0/3	1/3	0/3	2/10
Atrial fibrillationCardiac disorders	0/3	1/3	1/3	0/10
Left ventricular systolic dysfunctionCardiac disorders	0/3	1/3	0/3	0/10
AscitesGastrointestinal disorders	0/3	0/3	1/3	0/10

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Phase 1 Dose Level 1	Phase 1 Dose Level 2	Phase 1 Dose Level 3	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	Total
<=18 years	0	0	0	0	0
Between 18 and 65 years	1	1	1	4	7
>=65 years	2	2	2	6	12

Sex: Female, Male
Sex: Female, Male(Participants)	Phase 1 Dose Level 1	Phase 1 Dose Level 2	Phase 1 Dose Level 3	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	Total
Female	2	0	1	5	8
Male	1	3	2	5	11

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Phase 1 Dose Level 1	Phase 1 Dose Level 2	Phase 1 Dose Level 3	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	Total
Hispanic or Latino	0	1	0	0	1
Not Hispanic or Latino	3	2	2	10	17
Unknown or Not Reported	0	0	1	0	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Phase 1 Dose Level 1	Phase 1 Dose Level 2	Phase 1 Dose Level 3	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	1	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	0	0	0	0
White	3	2	3	10	18
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Phase 1 Dose Level 1	Phase 1 Dose Level 2	Phase 1 Dose Level 3	Phase 2 -Treatment at Maximum Tolerated Dose (MTD)	Total
United States	3	3	3	10	19

Study locations

1 site

Moffitt Cancer Center
Tampa, Florida 33612, United States

References and documents

Study documents

Protocol and statistical analysis plan · Mar 29, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 19, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04620681
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Responsible party: Sponsor
First posted: Nov 9, 2020
Start date: Jan 14, 2021
Primary completion: Jul 20, 2024
Completion: Jul 20, 2024
Results posted: Oct 22, 2025
Last update: Feb 19, 2026

Study contacts

Joseph Pidala, MD, PhD

principal investigator · Moffitt Cancer Center

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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