Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Biphenotypic, Acute

Lymphoma

Acute Disease

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Acute Leukemia of Ambiguous Lineage

Lymphosarcoma

Anti-Infective Agents

All Drugs and Chemicals

Cobicistat

Clotrimazole

Miconazole

Fluconazole

Antifungal Agents

Isavuconazole

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Cytochrome P-450 CYP3A Inhibitors

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in 1 of 6 dose-escalation arms:

* Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole
* Arm B: Participants receiving any strong CYP3A4 inhibitors for antifungal prophylaxis
* Arm C: Participants receiving revumenib and cobicistat
* Arm D: Participants receiving fluconazole for antifungal prophylaxis
* Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers
* Arm F: Participants receiving isavuconazole for antifungal prophylaxis

Phase 2: Oral revumenib; Following the determination of the RP2D in Phase 1, 3 indication-specific expansion cohorts will be enrolled as follows:

* Cohort 2A: Participants with KMT2Ar ALL/MPAL
* Cohort 2B: Participants with KMT2Ar AML
* Cohort 2C: Participants with NPM1m AML

revumenib

Phase 1 Arm C participants will receive 150 mg cobicistat daily.

cobicistat

Syndax Pharmaceuticals

Manjyot Nanhwan

Shirley Sian

George Yaghmour

Kyle Denzel Cobarrubias

Katelyn Anttila

Terri Peterson, RN

Shannon Gleason, MLS, CCRC

Aflac Cancer & Blood Disorders Center Referral

Howie Weiner, CCRP

David Dickens, MD

Morgan Johnson

Lindsay Rae

Hannah Hartman

Madeline Stowe

Kait Tkachuk

Karen Fehn

Joel Victor

Linda Brown

Kris Mahadeo

Nadia Osman

Molly Brandenburg

OHSU Knight Cancer Institute Clinical Trials

Ronan Swords, MD

Robin E Blauser, BSN RN

Ghayas Issa, MD

Farha Inam

Cathy Tran

Ashish Bajel

Shaun Fleming, MD

Carolyn Grove, MD

Matthew Greenwood, MD

Andre Schuh, MD

Aiman Siddiqi

Alexandre Deloire

Mael Heiblig

Mathilde Petit

Stephanie De Botton

Benjamin Bietsch

Melanie Koch

Hanoun Maher

Dirk Reinhardt

Berit Riemer

Annamaria Brioli

Conny Schuck

Michael Kuehn

Hadil Asadi

Baher Krayem

Dafna Laufer

Yishai Ofran

Leah Greenfeld

Boaz Nachmias

Lana Saada

Galia Stemer

Contact: Sharon Hercman Dachevsky

Ofir Wolach

Yuval Carmel

Irina Armitai

Francesco Ingletto

Cristina Papayannidis

Federica Frabetti

Giovanni Marconi

Irene Mutterle

Corinna Greco

Andrejus Cernovas

Andrius Zucenka

Secretary Trial and Data Centrum

Michael Zwaan

Anna Valer

Montserrat Arnan Sangerman

Laura More

Eduardo Rodriguez-Arboli

Elisa Gonzales

Pau Montesinos Fernandez

Angela R Smith, M.D.

Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia.

In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.

Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in one of six dose-escalation arms:

Arm A: Participants not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducers or fluconazole.

Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.

Arm C: Participants receiving revumenib and cobicistat.

Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.

Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.

Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.

In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib:

* Cohort 2A: Participants with KMT2Ar acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL)
* Cohort 2B: Participants with KMT2A AML
* Cohort 2C: Participants with NPM1m AML

Phase 1 will employ an accelerated titration design. The dose escalation will follow a modified Fibonacci sequence.

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX-5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation

Assessed by the NCI CTCAE version 5.0 (Phase 1)

Maximum plasma concentration (Cmax) of revumenib and relevant metabolites (Phase 1)

Time to observed maximum plasma concentration of revumenib and relevant metabolites (Phase 1)

Area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of revumenib and relevant metabolites (Phase 1)

To assess the complete remission (CR) and complete remission with partial hematologic recovery (CRh) rate (Phase 2)

Assessed by the NCI CTCAE version 5.0 (Phase 2)

Transfusion independence is defined as any transfusion-free period lasting for at least 56 consecutive days

To assess the composite definition of complete remission (CRc) rate (Phase 2)

To assess the overall response rate (ORR) of revumenib (Phase 2)

To assess the time to response (TTR) of revumenib (Phase 2)

To assess the duration of response (DOR) of revumenib (Phase 2)

To assess the event free survival (EFS) of revumenib (Phase 2)

To assess overall survival (OS) of revumenib (Phase 2)

Cmax of revumenib and relevant metabolites (Phase 2)

Tmax of revumenib and relevant metabolites (Phase 2)

AUC0-t of revumenib and relevant metabolites (Phase 2)

Hematologic Neoplasms

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
A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation	NCT04065399	Acute Myeloid L... Acute Lymphobla... Mixed Lineage A... Mixed Phenotype... Acute Leukemia ...	revumenib cobicistat	30 Days -	Syndax Pharmaceuticals
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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