Symptoms and General Pathology

All Conditions

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Syndrome

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Leukemia, Myeloid

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Myeloid Leukemia

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Cyclophosphamide

Fludarabine

Fludarabine phosphate

Thiotepa

Mesna

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Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

After meeting eligibility criteria and being enrolled, patients will receive:

Day -15 to -6 prior to hematopoietic stem cell transplant (HSCT), preparatory regimen of radiation and chemotherapy: Total Myeloid and Lymphoid Irradiation (TMLI): Days -15 to -11 prior to HSCT; - Chemotherapy (infusion): Day -10 to day -6 prior to HSCT: Fludarabine (all days), Thiotepa (days -10 and -9) and Cyclophosphamide and Mesna (days -8 and -7)

Day -4 prior to (HSCT), a Treg-enriched donor cell infusion and graft vs host disease (GVHD) assessment

Day -1 prior to (HSCT), a unmodified donor T Cell infusion and (GVHD) assessment

Day of (day 0) (HSCT), CD34+ Haplo Peripheral Blood Stem Cell Infusion/Transplant and (GVHD) assessment

Days 30, 60,100, 180, 365 post hematopoietic stem cell transplant (HSCT), participants will undergo testing and assessment of minimal residual disease (MRD) and (GVHD)

Total Myeloid and Lymphoid Irradiation (TMLI) delivered through Radiation Oncology institutional standards

Radiation

Given intravenously -10 to -6 days prior to hematopoietic stem cell transplant (HSCT)

Given intravenously on day -10 and day- 9 prior to hematopoietic stem cell transplant (HSCT)

Given intravenously with Mesna on day -8 and day- 7 prior to hematopoietic stem cell transplant (HSCT)

Given intravenously with Cyclophosphamide on day -8 and day -7 prior to hematopoietic stem cell transplant (HSCT)

Given intravenously -4 day prior to hematopoietic stem cell transplant (HSCT)

Treg-enriched donor cell

Given intravenously -1 day prior to hematopoietic stem cell transplant (HSCT)

Unmodified donor T Cell

CD34+ Haplo Peripheral Blood Stem Cell Transplantation

CD34+ Haplo Peripheral Blood Stem Cell

John Koreth, MBBS, DPhil

John Koreth, MD

This 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

This study is assessing whether the IS-free Treg-cell graft-engineered haplo HSCT) approach will reduce risk of relapse while preventing usual toxicities related to stem cell transplants (e.g., graft-versus-host-disease (GVHD)). GVHD is a complication of transplantation where the T cells (a type of white blood cell that helps protect the body from relapse by killing cancer cells) in the donor graft attack and damage some of the host tissues. Patients who receive an allogeneic (using another person as the donor) hematopoietic stem cell transplant (HSCT) may develop graft-versus-host disease (GVHD) toxicity and are also at risk of disease relapse.

The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive the study intervention Treg-enriched donor cells and will then be followed for 1 year after transplantation.

It is expected that about 20 people will take part in this research study.

Dana-Farber Cancer Institute research funds along with charitable donations are supporting this research study. Regeneron Pharmaceuticals, Inc. (a pharmaceutical company) is also supporting this research study by providing funding and support for correlative laboratory tests.

IS-free Treg HaploHCT

A Pilot/Phase 1 Study of Immunosuppression-free Regulatory T-cell Graft-engineered Haploidentical Hematopoietic Cell Transplantation in Relapsed/Refractory and Ultra-High-risk AML/MDS

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Safety will be assessed by dose-limiting toxicities (DLT) summarized by patient, type and grade as defined by the CTCAE v5.0.

Will be summarized descriptively and estimated in the competing risks framework treating death without GVHD or without engraftment as a competing event depending on the actual enrolled and evaluable number of patients.

Incidence of grade II-IV and III-IV acute graft vs host disease (GVHD) by day 180 after HCT

Will also be summarized descriptively, estimated in the competing risks framework treating each event as a competing event. Corresponding 95% CIs will be provided.

Estimated using Kaplan-Meier method with exact pointwise confidence intervals

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
IS-free Treg HaploHCT	NCT04678401	Stem Cell Trans... Graft Vs Host D... Myeloid Leukemi... Myeloid Leukemi... Myelodysplastic...	Radiation Fludarabine Thiotepa Cyclophosphamid... Mesna Treg-enriched d... Unmodified dono... CD34+ Haplo Per...	18 Years - 65 Years	Dana-Farber Cancer Institute
IS-free Treg HaploHCT	NCT04678401	Stem Cell Trans... Graft Vs Host D... Myeloid Leukemi... Myeloid Leukemi... Myelodysplastic...	Radiation Fludarabine Thiotepa Cyclophosphamid... Mesna Treg-enriched d... Unmodified dono... CD34+ Haplo Per...	18 Years - 65 Years	Dana-Farber Cancer Institute
IS-free Treg HaploHCT	NCT04678401	Stem Cell Trans... Graft Vs Host D... Myeloid Leukemi... Myeloid Leukemi... Myelodysplastic...	Radiation Fludarabine Thiotepa Cyclophosphamid... Mesna Treg-enriched d... Unmodified dono... CD34+ Haplo Per...	18 Years - 65 Years	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for cd34+ haplo peripheral blood stem cell