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OncoMatch/Clinical Trials/NCT04678401

IS-free Treg HaploHCT

Is NCT04678401 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies multiple treatments for stem cell transplant complications.

Phase 1RecruitingDana-Farber Cancer InstituteNCT04678401Data as of May 2026

Treatment: Mesna · Treg-enriched donor cell · Fludarabine · Thiotepa · Cyclophosphamide · Unmodified donor T Cell · MelphalanThis research study is evaluating the safety and efficacy of the IS-free Treg-cell graft-engineered haplo transplant method in people with relapsed/refractory and Ultra-high risk acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) receiving a haploidentical donor allogeneic hematopoietic stem cell transplant (HSCT). The names of the study interventions involved in this study are: * Radiation-Total Myeloid and Lymphoid Irradiation (TMLI) * Chemotherapy (Fludarabine, Thiotepa, Cyclophosphamide plus Mesna) * Infusion of haplo Treg-enriched donor cells (experimental therapy) * Infusion of unmodified haplo donor T cells (includes cancer-fighting T effector cells) * Infusion of haplo donor CD34+ Peripheral Blood Stem Cells

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Extracted eligibility criteria

Cancer type

Acute Myeloid Leukemia

Myelodysplastic Syndrome

Biomarker criteria

Required: TP53 any mutation

Ultra high-risk AML or MDS that meets definition of 'Myeloid Neoplasms with mutated TP53' per 2022 International Consensus Classification

Required: TP53 multi-hit or complex karyotype (CK+) mutated

Ultra high-risk AML or MDS that meets definition of 'Myeloid Neoplasms with multi-hit or complex karyotype (CK+) mutated TP53' per 2022 International Consensus Classification

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Min 1 prior line

Must have received: cytotoxic chemotherapy (3+7 chemotherapy, HMA therapy)

despite at least 1 prior line of therapy (e.g., 3+7 chemotherapy, HMA therapy)

Cannot have received: cytotoxic chemotherapy

Exception: hydroxyurea, HMA, FDA-approved novel targeted agents (e.g., venetoclax, FLT-3 inhibitors, IDH 1/2 inhibitors) permitted up to a day prior to start of HCT conditioning

Participants who have had cytotoxic chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or mitomycin C) prior to entering the study

Cannot have received: radiation therapy

Participants who have had cytotoxic chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or mitomycin C) prior to entering the study

Cannot have received: investigational agent

Exception: unless cleared by the study PI

Participants who are receiving any other investigational agents within 21 days (or 5 half-lives) prior to study entry, whichever is longer, unless cleared by the study PI

Cannot have received: Mylotarg or other therapies associated with increased risk of hepatic veno-occlusive disease (VOD) (Mylotarg)

Participants who received Mylotarg or other therapies associated with increased risk of hepatic veno-occlusive disease (VOD) or have known prior or active VOD

Cannot have received: allogeneic or autologous hematopoietic cell transplantation

Recipients of prior allogeneic or autologous hematopoietic cell transplantation, or solid organ transplantation

Cannot have received: solid organ transplantation

Recipients of prior allogeneic or autologous hematopoietic cell transplantation, or solid organ transplantation

Lab requirements

Blood counts

Adequate organ and marrow function as defined below

Kidney function

Serum Creatinine within normal institutional limits or creatinine clearance >50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal

Liver function

Total bilirubin within normal institutional limits (exception permitted in Gilbert's Syndrome after discussion with study PI, on a case-by-case basis); and AST (SGOT)/ALT (SGPT) <2x institutional upper limit of normal

Cardiac function

Cardiac Ejection Fraction ≥ 45%, and no evidence of pulmonary hypertension

Adequate organ and marrow function as defined below: Pulmonary Function: FEV1, FVC and DLCO ≥ 60% of predicted (corrected for hemoglobin) Cardiac Ejection Fraction ≥ 45%, and no evidence of pulmonary hypertension Hepatic: Total bilirubin within normal institutional limits (exception permitted in Gilbert's Syndrome after discussion with study PI, on a case-by-case basis); and AST (SGOT)/ALT (SGPT) <2x institutional upper limit of normal Renal: Serum Creatinine within normal institutional limits or creatinine clearance >50 mL/min/1.73 m2 (see Appendix B) for participants with creatinine levels above institutional normal.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Dana Farber Cancer Institute · Boston, Massachusetts

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