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Chemotherapy

Treg-Enriched Stem Cell Transplant for Leukemia

Phase 1

Recruiting

Led By John Koreth, MBBS, DPhil

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Cohort A: Histologically-confirmed disease in the prior 4 weeks, despite at least 1 prior line of therapy (e.g., 3+7 chemotherapy, HMA therapy): Rel/ref AML (de novo or secondary) with ≥5% blasts in BM (or extramedullary sites); MDS EB-2 (BM ≥10% blasts, PB 5-19% blasts). Cohort B: Ultra high-risk AML or MDS that meets definition of 'Myeloid Neoplasms with mutated TP53' per 2022 International Consensus Classification1 (Appendix L) regardless of response

Available haploidentical HLA-matched (-A, -B, -C, -DRB1) related donor aged 18-65 years

Must not have

Participants with uncontrolled bacterial, viral or fungal infections (i.e., currently taking medications with progression of clinical symptoms or signs)

Participants seropositive for hepatitis B or C infection are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after myeloablative HCT

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 30 days after hematopoietic cell transplantation (hct)

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying a new way to give a haploidentical stem cell transplant (using donor cells that have been enriched with regulatory T cells) to people with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome.

Who is the study for?

Adults aged 18-65 with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), who have a compatible family donor, can join this trial. Participants need good heart, lung, and kidney function and must not be pregnant or breastfeeding. They should agree to use contraception during the study.

What is being tested?

The trial is testing an experimental stem cell transplant method using radiation, chemotherapy (Fludarabine, Thiotepa, Cyclophosphamide plus Mesna), and infusions of Treg-enriched donor cells along with unmodified haplo donor T cells and CD34+ Peripheral Blood Stem Cells in patients with AML/MDS.

What are the potential side effects?

Potential side effects include reactions to the infusion of cells, organ damage from radiation or chemotherapy drugs like Fludarabine and Cyclophosphamide. There's also a risk of infection due to immune system suppression by treatments.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a related donor aged 18-65 who is a partial HLA match.

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I am between 18 and 65 years old.

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My kidney function is within the normal range.

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I can take care of myself but might not be able to do active work.

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My heart pumps well and I don't have high blood pressure in my lungs.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any uncontrolled infections.

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I do not have hepatitis B or C.

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I do not have cancer in areas like the brain, eyes, or testes.

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I cannot undergo intense radiation due to a previous condition or exposure.

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I do not have significant donor-specific antibodies that require treatment.

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I have a history of blood clotting disorders like TMA or HUS/TTP.

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I haven't had certain cancer treatments in the last 2 to 4 weeks, but I may have been on specific approved medications until recently.

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I am not pregnant and not breastfeeding if I plan to undergo treatment.

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I have had a bone marrow or organ transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 30 days after hematopoietic cell transplantation (hct)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~30 days after hematopoietic cell transplantation (hct)

This trial's timeline: 3 weeks for screening, Varies for treatment, and 30 days after hematopoietic cell transplantation (hct) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting toxicities (DLT)

Secondary study objectives

Engraftment rate

Mortality Rate-GVHD Non- Relapse

Graft-vs-Host Disease

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: IS-FREE TREG CRAFT_ENGINEERED HaploHCT for relapsed/refractory AML or MDS EB-2 (Closed to Accrual)Experimental Treatment8 Interventions

Please note that this arm is closed due to meeting accrual goal as of June 2024. 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)

Group II: IS-FREE TREG CRAFT_ENGINEERED HaploHCT for Ultra high-risk AML or MDS with mutated TP53Experimental Treatment8 Interventions

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)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Mesna

2003

Completed Phase 2

~1380

Cyclophosphamide

2010

Completed Phase 4

~2310

Radiation

2003

Completed Phase 2

~780

Fludarabine

2012

Completed Phase 4

~1860

Thiotepa

2008

Completed Phase 3

~2120

0 / 15Eligibility criteria met

Find a Location

Who is running the clinical trial?

Dana-Farber Cancer InstituteLead Sponsor

1,113 Previous Clinical Trials

358,729 Total Patients Enrolled

John Koreth, MBBS, DPhilPrincipal Investigator - Dana-Farber Cancer Institute

Dana-Farber Cancer Institute

Maulana Azad Medical College (Medical School)

Brigham & Women'S Hospital (Residency)

5 Previous Clinical Trials

141 Total Patients Enrolled

Media Library

$Myelodysplastic Syndrome Research Study Groups: IS-FREE TREG CRAFT_ENGINEERED HaploHCT for relapsed/refractory AML or MDS EB-2 (Closed to Accrual), IS-FREE TREG CRAFT_ENGINEERED HaploHCT for Ultra high-risk AML or MDS with mutated TP53$