Refractory Acute LeukemiaPhase 1NCT06397027
A Phase I Study Investigating the Combination of the Ziftomenib, Venetoclax and Azacitidine in Pediatric Relapsed and Refractory Acute Leukemias
A Phase 1 study testing Ziftomenib, Venetoclax and Azacitidine in people with Refractory Acute Leukemia and Pediatric Relapsed, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Refractory Acute Leukemia, Pediatric Relapsed
- What is being tested?
- Ziftomenib, Venetoclax and Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Dec 2024to 31 Dec 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 2 year to 21 years
- ECOG performance status of ≤ 2.
- Relapsed/refractory: AML60, Mixed phenotype acute leukemia61 (MPAL), ALL61, Acute leukemia of ambiguous lineage (ALAL)62 patients with KMT2A-r, NPM1-m, NUP98-r, or HOX pathway mutation as detailed in background section
- ≥5% leukemic blasts in the bone marrow:
- WBC must be below 25 K/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
- Baseline ejection fraction must be > 40%.
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- Adequate hepatic function (direct bilirubin < 1.5x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT < 5x ULN unless considered due to leukemic involvement, in which case direct bilirubin < 3x ULN or AST and/or ALT < 5x ULN will be considered eligible).
- Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease. (Justification on page 11)
- In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy (whichever is shorter). Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
- Unless surgically or biologically sterile: Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months for males, and 6 months for females, after the last treatment.
Who cannot join
- Participants who weigh less than 10kg.
- Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
- The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
- Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
- Participants with a concurrent active malignancy under treatment.
- Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or active/uncontrolled HIV infection, AIDS, or currently taking contraindicated medications for HIV control.
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- Female participants who are pregnant or breast-feeding.
- Participant has an active uncontrolled infection.
- Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class .II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
- Corrected QT interval by Fredericia's formula >480 ms on 12-lead electrocardiograms.
- History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate.
- Clinically active central nervous system (CNS) leukemia.
- The use of topical steroids for cutaneous graft-versus-host disease (GVHD) or stable systemic steroid doses less than or equal to 20 mg of prednisone daily are permitted.
- Participants with Grade > 2 active acute GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
- Has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the first dose of venetoclax.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
David McCall, MD, 713-792-6604, dmccall1@mdanderson.org
David McCall, MD
About this study
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).
Read the detailed description
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, NUP98-r, or HOX pathway mutations.
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.
- To investigate relationships between PK/exposure and clinical outcomes (e.g.,safety/tolerability, efficacy).
- Conditions
- Refractory Acute Leukemia, Pediatric Relapsed
- Being tested
- Ziftomenib, Venetoclax, Azacitidine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZiftomenibDrug
Given by IV
VenetoclaxDrug
Also called ABT-199, GDC-0199
Given by PO
AzacitidineDrug
Also called 5-azacytidine,, 5-aza, Vidaza™, 5-AZC
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Dose-escalation + Dose-expansion of Ziftomenib | Experimental | 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. Receives: Drug: Ziftomenib; Drug: Venetoclax; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2024
- Study start27 Dec 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Acute LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Kura Oncology, Inc.
- Responsible party
- Sponsor
- Investigators
- David McCall, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06397027
- Sponsor's protocol ID
- 2023-1008
- Other IDs
- NCI-2024-03798
- Status last verified
- Sep 2026
- First submitted
- 30 Apr 2024
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Investigating the Combination of the Ziftomenib, Venetoclax and Azacitidine in Pediatric Relapsed and Refractory Acute Leukemias
- ClinicalTrials.gov ID
- NCT06397027
- Acronym / sponsor ID
- 2023-1008
- Conditions
- Refractory Acute Leukemia, Pediatric Relapsed
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Kura Oncology, Inc.
- Study start
- 27 Dec 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 2 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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, NUP98-r, or HOX pathway mutations.
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.
- To investigate relationships between PK/exposure and clinical outcomes (e.g.,safety/tolerability, efficacy).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation + Dose-expansion of Ziftomenib | Experimental | Drug: Ziftomenib, Drug: Venetoclax, Drug: AzacitidineThe 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. |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Age ≥ 2 year to 21 years
- ECOG performance status of ≤ 2.
- Relapsed/refractory: AML60, Mixed phenotype acute leukemia61 (MPAL), ALL61, Acute leukemia of ambiguous lineage (ALAL)62 patients with KMT2A-r, NPM1-m, NUP98-r, or HOX pathway mutation as detailed in background section
- WBC must be below 25 K/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
- Baseline ejection fraction must be > 40%.
Key exclusion criteria (15 listed)
- Participants who weigh less than 10kg.
- Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
- The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
- Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
- Participants with a concurrent active malignancy under treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZiftomenibGiven by IV | Drug | Dose-escalation + Dose-expansion of Ziftomenib |
| VenetoclaxAlso: ABT-199, GDC-0199Given by PO | Drug | Dose-escalation + Dose-expansion of Ziftomenib |
| AzacitidineAlso: 5-azacytidine,, 5-aza, Vidaza™, 5-AZCGiven by PO | Drug | Dose-escalation + Dose-expansion of Ziftomenib |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David McCall, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ziftomenib, Venetoclax and Azacitidine in people with Refractory Acute Leukemia and Pediatric Relapsed, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David McCall, MD ((713) 792-6604, dmccall1@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.