A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML

Conditions

• AML With Mutated NPM1
• Acute Myeloid Leukemia
• Acute Myeloid Leukemia Recurrent
• Acute Myeloid Leukemia, in Relapse
• KMT2Ar
• Mixed Lineage Leukemia Gene Mutation
• Myeloid Sarcoma
• NPM1 Mutation
• Nucleophosmin 1-mutated Acute Myeloid Leukemia
• Refractory AML

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Ziftomenib — DRUG
  Oral Administration
• Venetoclax — DRUG
  Oral Administration
• Azacitidine — DRUG
  Subcutaneous or Intravenous Administration
• Daunorubicin — DRUG
  Intravenous Administration
• Cytarabine — DRUG
  Intravenous Administration
• Quizartinib — DRUG
  Oral Administration

Study Details

Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with certain genetic alterations. This protocol has 3 separate arms that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) drug treatments in patients who have AML with certain genetic mutations. Both newly diagnosed and relapsed refractory patients with AML will be assigned to different cohorts based on specific study criteria and physician discretion. The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to treat AML.

Key Dates

Start date

Jul 18, 2023

Status verified

Mar 2026

Primary completion

Apr 30, 2030

Completion

Apr 30, 2030

Study Design

Enrollment

420 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1)
  Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
• Experimental: Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1)
  Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
• Experimental: Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2)
  Ziftomenib with 7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and must be FLT3 wildtype or ITD ratio \<0.05
• Experimental: Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2)
  Ziftomenib with 7+3 in newly diagnosed NPM1-m AML patients who are candidates for intensive chemotherapy and must be FLT3 wildtype or ITD ratio \<0.05
• Experimental: Dose Validation/Expansion: Ziftomenib with Venetoclax in R/R NPM1-m (A-3)
  Ziftomenib with Venetoclax in relapsed/refractory NPM1-m AML patients who have failed at least one prior line of therapy
• Experimental: Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4)
  Ziftomenib with Venetoclax and Azacitidine in newly diagnosed NPM1-m AML patients
• Experimental: Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1)
  Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy
• Experimental: Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1)
  Ziftomenib with Venetoclax and Azacitidine in relapsed/refractory KMT2A-r AML patients who have failed at least one prior line of therapy
• Experimental: Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2)
  Ziftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive chemotherapy
• Experimental: Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2)
  Ziftomenib with 7+3 in newly diagnosed KMT2A-r AML patients who are candidates for intensive therapy
• Experimental: Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3)
  Ziftomenib with Venetoclax and Azacitidine in newly diagnosed KMT2A-r AML patients
• Experimental: Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1)
  Ziftomenib with 7+3 and quizartinib in newly diagnosed NPM1-m and FLT3-ITD+ (with allelic ratio ≥0.05) AML patients who are candidates for IC and eligible to receive FLT3-targeted therapy
• Experimental: Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1)
  Ziftomenib with 7+3 and quizartinib in newly diagnosed NPM1-m and FLT3-ITD+ (with allelic ratio ≥0.05) AML patients who are candidates for IC and eligible to receive FLT3-targeted therapy

Primary Outcome Measure

Rate of dose limiting toxicities (DLTs) per dose level (Part 1a only) [ Time Frame: During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle) ]

Central Contacts

• Kura Medical Information
  844-KURAONC
  [email protected]

Locations (44)

Find similar trials in Phoenix, AZ

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