Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Neoplasms

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Cytarabine

Fludarabine

Fludarabine phosphate

Lenograstim

Gilteritinib

Idarubicin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Adjuvants, Immunologic

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Oral ziftomenib; sequential cohorts of escalating dose levels of ziftomenib to identify the safety and tolerability of the combination regimens. Participants will be enrolled in 1 of 5 dose escalation cohorts:

A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA

A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC)

A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib

B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA

B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)

Oral ziftomenib; Following the determination of the maximum tolerated dose in Phase 1a, participants will be enrolled in 1 of 5 dose validation/expansion cohorts:

A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA

A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC)

A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib

B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA

B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)

Ziftomenib

Granulocyte colony-stimulating factor

Clinical Operations

Farah Fasihuddin

KUCC Navigation Team

Cathy Galasso

Kristyn Dailey

Aaron Goldberg, MD, PhD

Cynthia J Lowery

Lisa Johnson

Fiona Davidson

Allison Pike

Ghayas C Issa, MD

Clinical Development

The safety, tolerability, and antileukemic response of ziftomenib in combination with standard of care treatments for patients with relapsed/refractory acute myeloid leukemia will be examined with the following agents: FLAG-IDA, low-dose cytarabine, and gilteritinib.

Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Phase 1 Study to Determine the Safety and Tolerability of Ziftomenib Combinations for the Treatment of KMT2A-rearranged or NPM1-mutant Relapsed/Refractory Acute Myeloid Leukemia

To assess proportion of patients alive at 6 months

To assess minimum residual disease in bone marrow as assessed by multiparameter flow cytometry (MFC) and molecular analysis

To assess proportion of patients that undergo a hematopoietic stem-cell transplant

To assess rate of transfusion independence

To assess the maximum plasma combination of ziftomenib and its metabolites

To assess the time to observed maximum plasma concentration of ziftomenib and its metabolites

To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of ziftomenib and its metabolites

To assess the area under the plasma concentration-time-curve over a dosing interval for ziftomenib and its metabolites

To assess the maximum plasma combination of gilteritinib

To assess the time to observed maximum plasma concentration of gilteritinib

To assess the area under the plasma concentration-time-curve from time 0 to time of last measurable concentration of gilteritinib

To assess the area under the plasma concentration-time-curve over a dosing interval for gilteritinib

Kura Oncology, Inc.

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

ziftomenib

Kura Oncology Expanded Access

Requests for single patient expanded access to ziftomenib monotherapy may be considered for eligible adult patients with Acute Lymphoblastic Leukemia (ALL), with appropriate mutations, or Acute Myeloid Leukemia (AML), with NPM1 mutations.

To request access, use Responsible Party contact information provided in this record.

Expanded access for ziftomenib is only available in the United States

Expanded Access to Ziftomenib

Symptoms and General Pathology

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

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

Venetoclax

Azacitidine

Decitabine

The first group of 3 participants will receive the starting dose of ziftomenib. If no intolerable side effects are seen, the rest of the study participants will receive a higher dose of ziftomenib. If intolerable side effects were seen at the starting dose, the next group of 3 participants will receive a lower total dose given for a shorter time period. If needed for safety, an even lower total dose schedule can be assigned to the next group of participants.

David McCall, MD

To find the highest safe dose of ziftomenib that can be combined with venetoclax and azacitidine in pediatric participants with acute leukemia that has certain types of genetic mutations (changes).

Primary Objectives

- To determine the safety, tolerability, and recommended Phase II dose (RP2D) of ziftomenib in combination with venetoclax and azacitidine for pediatric participants with acute leukemias with KMT2A-r, NPM1-m or NUP98-r.

Secondary Objectives - To determine the preliminary assessment of efficacy by overall response (OR), including complete remission (CR), CR with partial hematological recovery (CRh), CR with incomplete blood count recovery (CRi), morphological leukemia-free state (MLFS) and partial remission (PR), overall survival (OS), event-free survival (EFS) and duration of response (DOR) of pediatric participants treated with this combination.

Exploratory Objective

- To evaluate molecular and cellular markers that may be predictive of antitumor activity and/or resistance.

A Phase I Study Investigating the Combination of the Ziftomenib, Venetoclax and Azacitidine in Pediatric Relapsed and Refractory Acute Leukemias

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia	NCT06001788	AML AML With Mutate... Hematologic Mal... KMT2Ar NPM1 Mutation MLL Rearrangeme... Leukemia Acute Myeloid L... Leukemia, Myelo... Leukemia, Myelo... Acute Leukemia Neoplasms by Hi...	Ziftomenib Fludarabine Idarubicin Cytarabine Gilteritinib Granulocyte col...	18 Years -	Kura Oncology, Inc.
Expanded Access to Ziftomenib	NCT05738538	Acute Lymphobla... Acute Myeloid L...	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.
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.
A Phase I Study Investigating the Combination of the Ziftomenib, Venetoclax and Azacitidine in Pediatric Relapsed and Refractory Acute Leukemias	NCT06397027	Refractory Acut... Pediatric Relap...	Ziftomenib Venetoclax Azacitidine	2 Years - 21 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for ziftomenib

Every month we try and update this database with for ziftomenib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ziftomenib

Every month we try and update this database with for ziftomenib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ziftomenib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.