Symptoms and General Pathology

All Conditions

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Rare Diseases

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Lymphoma

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Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

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Leukemia, Myeloid

Leukemia, Myeloid, Acute

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Myelodysplastic Syndromes

Burkitt Lymphoma

Leukemia, Myelomonocytic, Juvenile

Neoplasms by Histologic Type

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Lymphoma, B-Cell

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Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Myeloid Leukemia

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Myelodysplastic/myeloproliferative Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Busulfan

Thiotepa

Standard of care myeloablative regimens will be used based on disease type and clinical status at time of transplant. Patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma will receive total body irradiation (TBI) regimen (thiotepa, cyclophosphamide, TBI).

Standard of care myeloablative regimens will be used based on disease type and clinical status at time of transplant. Patients not diagnosed with ALL or lymphoblastic lymphoma may receive either total body irradiation (TBI) regimen (thiotepa, cyclophosphamide, TBI) or busulfan containing regimen (thiotepa, cyclophosphamide, busulfan).

Peripheral stem cell (PSC) product will be processed using the CliniMACS device for TCRαβ and T cell depletion. Approximately 10% of the PSCs will undergo CD45RA depletion and cryopreservation. Patients will receive CD45RA depleted infusion after the TCRab PSCT.

CliniMACS Cell Processing System for TCRαβ + T Cell and CD45RA Depleted Peripheral Stem Cell Addback

Patricia Hankins, BSN, RN, CCRC

Meghan Rys, MS, CCRP

Nancy Bunin, MD

The major morbidities of allogeneic hematopoietic stem cell transplant with non-human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life threatening infections. T depletion of the donor hematopoietic stem cell graft is effective in preventing GVHD, but immune reconstitution is slow, increasing the risk of infections. An addback of donor CD45RA (naive T cells) depleted cells may improve immune reconstitution and help decrease the risk of infections.

The risk of severe graft versus host disease (GVHD) is increased with the use of unrelated and partially matched related donors. T cell depletion reduces the risk of severe GVHD, but immune reconstitution is delayed. Important memory T cells that may protect patients from fungal and viral infections are also removed in the T depletion process. CD45RA depletion has been studied both as a single step to reduce the risk of GVHD, and also, in conjunction with αβTCR depleted hematopoietic stem cell grafts to accelerate immune reconstitution. This is a single institutional pilot trial of this T cell depletion technique. Patients with acute leukemias at high risk for relapse are eligible to participate. Patients will be given CD45RA depleted donor peripheral stem cells (PSCs) following T depleted hematopoietic stem cell transplant (HSCT). A short course of GVHD prophylaxis will be used after CD45RA depletion.

CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT

CD45RA Depleted Peripheral Stem Cell Addback for Patients at Risk for Viral or Fungal Infections Post TCRαβ/CD19 Depleted Hematopoietic Stem Cell Transplant

Incidence of acute graft vs. host disease (GVHD) (reaction of donor immune cells against host tissues)

Children's Hospital of Philadelphia

BMT Medical Director

Hematologic Neoplasms

Leukemia, Biphenotypic, Acute

Acute Disease

Disease Attributes

Acute Leukemia of Ambiguous Lineage

Cohort 1: KMT2A-r / NPM1-m patients will receive a dose previously studied in Phase 1a

Cohort 2: KMT2A-r / NPM1-m patients will receive a dose previously studied in Phase 1a

NPM1-m patients will receive the recommended phase 2 dose determined in Phase 1

Ziftomenib

Clinical Operations

Joshua Sandolo

Christine Duran

Bruck Habtemariam

Jill Weisenbach, RN

Larissa Sanglard, MD

Christine Connolly

Emily Tolksdorf

Cancer Center Clinical Trials Referral Office

Lumi Demirovic

Tania Curcio

Tina Czaplinska

hematologyresearch@duke.edu

Silas Day

Felicia Kass

Recruitment and Eligibility Office

Yasmeen Akhtar, MBBS,MS,CCRP

Rachel Abramowicz

This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess ziftomenib, a menin-MLL(KMT2A) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML) as part of Phase 1. In Phase 2, assessment of ziftomenib will continue in patients with NPM1-m AML.

This Phase 1/2, first-in-human (FIH), open-label, dose-escalation and dose-validation/expansion study will assess ziftomenib, a menin-MLL(KMT2A) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML).

The dose-escalation part of the study (Phase 1a) will determine the maximal tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D).

The dose-validation/expansion part of the study (Phase 1b) will determine the safety, tolerability, and minimal biologically effective dose of ziftomenib in dosing cohorts which have demonstrated early biological activity and have been determined to be safe in the dose-escalation phase.

The Phase 2 portion of the study will determine the safety, tolerability, and anti-leukemia activity of ziftomenib in patients with NPM1-m AML.

First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1/2 First in Human Study of the Menin-MLL(KMT2A) Inhibitor KO-539 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

MTD is defined as the highest dose that is not expected to cause dose limiting toxicity (DLT) in more than 20% of patients.

Minimal biologically effective dose in dosing cohorts which have demonstrated biological activity and have been determined to be safe as a part of Part 1a

Anti-leukemia activity is assessed by the CR (CR+CRh) rate

Time to observed maximum plasma concentration of ziftomenib and/or its metabolites

Area under the plasma concentration-time curve from time 0 to time of last measurable concentration of ziftomenib and/or its metabolites

Maximum plasma concentration of ziftomenib and/or its metabolites

To assess the CR rate with and without MRD

Kura Oncology, Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT	NCT03810196	Acute Leukemia Acute Myeloid L... Myelodysplastic... Acute Lymphobla... Mixed Lineage L... Lymphoblastic L... Burkitt Lymphom... Juvenile Myelom...	CliniMACS Cell ...	- 25 Years	Children's Hospital of Philadelphia
First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia	NCT04067336	Advanced Malign... Acute Myeloid L... Mixed Lineage L... Mixed Lineage A... Acute Leukemia ... Mixed Phenotype...	Ziftomenib	18 Years -	Kura Oncology, Inc.
First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia	NCT04067336	Advanced Malign... Acute Myeloid L... Mixed Lineage L... Mixed Lineage A... Acute Leukemia ... Mixed Phenotype...	Ziftomenib	18 Years -	Kura Oncology, Inc.

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