Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Dermatologic Agents

Etoposide

Cytarabine

Etoposide phosphate

Tretinoin

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Keratolytic Agents

6 cycles of chemotherapy (low-dose cytarabine and etoposide) without ATRA

6 cycles of chemotherapy (low-dose cytarabine and etoposide) with ATRA (All-trans-Retinoic acid)

in all treatment cycles: Cytarabine 20 mg/day, s.c., bid, days 1-7; (total dose 280 mg).

first treatment cycle Etoposide 50 mg/m²/day, continuously i.v., days 1-3; (total dose 150 mg/m2) treatment cycles 2 to 6 Etoposide 100 mg/day, p.o. or i.v. (over 1 hour), days 1-3; (total dose 300 mg).

in all treatment cycles: ATRA 45 mg/m²/day p.o., days 8-10, ATRA 15 mg/m²/day p.o., days 11-28, with or shortly after meals distributed on 3 doses per day.

All-trans retinoic acid (ATRA)

Hartmut Döhner, MD

This is a randomized, Phase-III, two-arm, open-label, multi-center study in adult patients with AML and NPM1 mutation ineligible for intensive chemotherapy.

Sample size: 144 patients

Investigator's sites: 50-55 sites in Germany and Austria (2-10 patients per trial site are expected to be included into the trial)

Estimated treatment duration of an individual patient: 8 months (Follow-Up period per patient will last additional 2 years)

Study of Low-Dose Cytarabine and Etoposide With or Without All-Trans Retinoic Acid in Older Patients Not Eligible for Intensive Chemotherapy With Acute Myeloid Leukemia and NPM1 Mutation

adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 4.0

assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30), supplemented by information on self-assessed concomitant diseases, late treatment effects, and demographics according to Messerer et al.33

German Federal Ministry of Education and Research

University of Ulm

Prof. Dr.

Idarubicin

Gemtuzumab

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

chemotherapy in combination with ATRA with gemtuzumab ozogamicin

chemotherapy in combination with ATRA without gemtuzumab ozogamicin

Induction Cycle 1, 2: GO 3mg/m² by intravenous infusion (IVI) on day 1 (total dose 3 mg/m2). Start after etoposide IVI. No dose reduction is foreseen in elderly (\> 60 yrs) patients.

Consolidation 1: GO 3mg/m² by intravenous infusion (IVI) on day 1 (total dose 3 mg/m2). Start after first dose of high-dose cytarabine. No dose reduction is foreseen in elderly (\> 60 yrs) patients.

For all patients experiencing prolonged thrombocytopenia CTC-Grade 3/4 during the first or second induction therapy, which occurs for more than day 35 after start of the cycle, the further cycles of therapy will be administered without Gemtuzumab ozogamicin.

Consolidation 2, 3: no GO

Gemtuzumab Ozogamicin (Mylotarg)

Idarubicin, Etoposide, Cytarabine, ATRA, Pegfilgrastim

standard chemotherapy

Hartmut Doehner, MD

Randomized Phase-III, two-arm, open-label, multi-center study in adult patients with AML and NPM1 mutation.

Before Amendment No. 4 (December 2013):

Primary Efficacy Objective:

* Evaluation of efficacy based on event-free survival (EFS) after induction and consolidation chemotherapy plus all-trans retinoic acid (ATRA) with or without gemtuzumab ozogamicin (GO) in adult patients with acute myeloid leukemia (AML) and mutant nucleophosmin-1 (NPM1)

After Amendment No. 4 (December 2013):

Primary Efficacy Objective:

* Evaluation of efficacy based on overall survival (OS) after induction and consolidation chemotherapy plus all-trans retinoic acid (ATRA) with or without gemtuzumab ozogamicin (GO) in adult patients with acute myeloid leukemia (AML) and mutant nucleophosmin-1 (NPM1)

Study of Chemotherapy in Combination With All-trans Retinoic Acid (ATRA) With or Without Gemtuzumab Ozogamicin in Patients With Acute Myeloid Leukemia (AML) and Mutant Nucleophosmin-1 (NPM1) Gene Mutation

Phase III Study of Chemotherapy in Combination With ATRA With or Without Gemtuzumab Ozogamicin in Patients With Acute Myeloid Leukemia and NPM1 Gene Mutation

Hematologic Neoplasms

Amino Acids

Fludarabine

Fludarabine phosphate

Lenograstim

Gilteritinib

Adjuvants, Immunologic

Anti-Bacterial Agents

Antibiotics, Antitubercular

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.

Symptoms and General Pathology

Disease Progression

Recurrence

Disease Attributes

Venetoclax

Azacitidine

subjects will receive treatment until alloSCT

subjects will receive venetoclax 400 mg orally QD on Days 1 - 28 plus azacitidine 75 mg/m2 SC or IV daily for 7 days. Cycle Length - 28 Days. . Subjects will continue treatment until subsequent alloSCT.

Venetoclax+azacitidine

Paola Fazi

Enrico Crea

Antonio Curti

This is a phase 2, non-randomized, interventional, open-label, multicenter trial evaluating the efficacy of VEN-AZA as a bridge-to-transplant therapy in chemotherapy-treated adult NPM1mut AML patients who experience molecular relapse or progression during treatment or follow-up. Subjects will receive cycles of venetoclax plus azacitidine. After each cycle, MRD will be evaluated and at any time of MRD-negativity, AlloSCT will be performed.

This is a phase 2, non-randomized, interventional, open-label, multicenter trial evaluating the efficacy of VEN-AZA as a bridge-to-transplant therapy in chemotherapy-treated adult NPM1mut AML patients who experience molecular relapse or progression during treatment or follow-up.

Subjects will receive venetoclax 400 mg orally QD on Days 1 - 28 plus azacitidine 75 mg/m2 SC or IV daily for 7 days. Cycle Length: 28 Days.

Subjects will continue treatment until subsequent alloSCT, documented morphological bone marrow and/or extramedullary disease progression, toxicity, withdrawal of consent, or the subject meets other protocol criteria for discontinuation (whichever occurs first).

After each cycle, MRD will be evaluated. AlloSCT is recommended at any time of MRD-negativity. After 6 cycles of treatment, regardless MRD status, patients will proceed to alloSCT.

Venetoclax and Azacitidine for the Management of Molecular Relapse/Progression in Adult NPM1-mutated Acute Myeloid Leukemia

A Multicentric Phase 2 Study of Venetoclax and Azacitidine for the Management of Molecular Relapse/Progression in Adult NPM1-MUTATED Acute Myeloid Leukemia

Evaluation of treatment efficacy in terms of percentage of patients who do not experience overt relapse at 6 months or within stem cell transplant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Low-Dose Cytarabine and Etoposide With or Without All-Trans Retinoic Acid in Older Patients Not Eligible for Intensive Chemotherapy With Acute Myeloid Leukemia and NPM1 Mutation	NCT01237808	Acute Myeloid L...	Cytarabine Etoposide All-trans retin...	61 Years -	University of Ulm
Study of Chemotherapy in Combination With All-trans Retinoic Acid (ATRA) With or Without Gemtuzumab Ozogamicin in Patients With Acute Myeloid Leukemia (AML) and Mutant Nucleophosmin-1 (NPM1) Gene Mutation	NCT00893399	Acute Myeloid L...	Gemtuzumab Ozog... standard chemot...	18 Years -	University of Ulm
Study of Low-Dose Cytarabine and Etoposide With or Without All-Trans Retinoic Acid in Older Patients Not Eligible for Intensive Chemotherapy With Acute Myeloid Leukemia and NPM1 Mutation	NCT01237808	Acute Myeloid L...	Cytarabine Etoposide All-trans retin...	61 Years -	University of Ulm
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.
Venetoclax and Azacitidine for the Management of Molecular Relapse/Progression in Adult NPM1-mutated Acute Myeloid Leukemia	NCT04867928	Acute Myeloid L... Acute Myeloid L... NPM1 Mutation	Venetoclax+azac...	18 Years -	Gruppo Italiano Malattie EMatologiche dell'Adulto

Spots Global Cancer Trial Database for npm1 mutation