A Phase 1B/2A Trial of Combination of ASTX727 With ASTX029 in Acute Myeloid Leukemia

NCT06113289 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2022-0840NCI-2023-09243
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To find the recommended dose of the study drugs ASTX727 and ASTX029 that can be given to patients with relapsed/refractory AML. The goal of Part 2 of the study is to learn if the dose of study drugs found in Part 1B can help to control AML.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 \[Time Frame: through study completion; an average of 1 year.\]

  Through study completion; an average of 1 year.

Study Arms (2)

Part 1B

EXPERIMENTAL

During cycle 1: Participants will take: ASTX029 tablets daily by mouth on days 1-42. ASTX727 tablets by mouth 1 time every day on Days 15-19. You should take ASTX727 and ASTX029 fasting (about 2 hours before a meal, and 2 hours after a meal). Cycles 2 and beyond: Participants will take ASTX029 tablets by mouth every day (days 1-28) fasting, (2 hours before and 2 hours after a meal). You will also take ASTX727 tablets by mouth 1 time every day on days 1-5 of each cycle, fasting (2 hours before and 2 hours after a meal).

Drug: ASTX727; Drug: ASTX029-01

Part 2

EXPERIMENTAL

During cycle 1: Participants will take: ASTX029 tablets daily by mouth on days 1-42. ASTX727 tablets by mouth 1 time every day on Days 15-19. You should take ASTX727 and ASTX029 fasting (about 2 hours before a meal, and 2 hours after a meal). Cycles 2 and beyond: Participants will take ASTX029 tablets by mouth every day (days 1-28) fasting, (2 hours before and 2 hours after a meal). You will also take ASTX727 tablets by mouth 1 time every day on days 1-5 of each cycle, fasting (2 hours before and 2 hours after a meal).

Drug: ASTX727; Drug: ASTX029-01

Interventions

ASTX727 DRUG

Given by PO

Also known as: Inqovi

Part 1B; Part 2

ASTX029-01 DRUG

Given by PO

Part 1B; Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1B: Diagnosis of relapsed/refractory AML (excluding acute promyelocytic leukemia)
• Phase 2A: Diagnosis of relapsed/refractory AML (excluding acute promyelocytic leukemia) with MAPK pathway mutations e.g. N or KRAS, PTPN11, NF1 etc.
• Patients aged ≥18 years old with relapsed/refractory AML with MAPK pathway mutations e.g. N or KRAS, PTPN11, NF1 etc. are eligible if they are not eligible for potentially curative therapy such as more effective salvage therapy or hematopoietic stem cell transplantation or who refuse these options at the time of enrollment.
• Patient must be receiving protocol therapy as salvage 1 or 2.
• Phase 1B: Diagnosis of relapsed/refractory AML (excluding acute promyelocytic leukemia)
• Phase 2A: Diagnosis of relapsed/refractory AML (excluding acute promyelocytic leukemia) with MAPK pathway mutations e.g. N or KRAS, PTPN11, NF1 etc.
• Patients aged ≥18 years old with relapsed/refractory AML with MAPK pathway mutations e.g. N or KRAS, PTPN11, NF1 etc. are eligible if they are not eligible for potentially curative therapy such as more effective salvage therapy or hematopoietic stem cell transplantation or who refuse these options at the time of enrollment.
• Patient must be receiving protocol therapy as salvage 1 or 2.
• Patients aged ≥ 18 years old, with MDS or CMML treated with hypomethylating agent (HMA) therapies who progress to AML and have no available therapies or are not candidates for available therapies, will be eligible at the time of progression to AML.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2
• Temporary prior measures such as apheresis while eligibility work-up is being performed are allowed and not counted as a prior salvage
• In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of protocol therapy will be at least 2 weeks or at least 5 half-lives (whichever is longer). The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator's brochures, or drug-administration manuals) and will be documented in the protocol eligibility document.
• The toxicity from prior therapy should have resolved to Grade ≤1, however alopecia and sensory neuropathy Grade ≤2 not constituting a safety risk based on investigators judgement is acceptable.
• The use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following c: (1) intrathecal (IT) therapy for patients with controlled CNS leukemia at the discretion of the PI. (2) Use of 1-2 doses of cytarabine (up to 1.5 g/m2 each dose) for patients with rapidly proliferative disease is allowed up to 7 days before the start of study therapy (7 days washout). Since the anti-leukemia effect of HMA-therapies and kinase inhibitors may be delayed, use of hydroxyurea for patients with rapidly proliferative disease is allowed on study and before the start of study therapy and will not require a washout. These medications will be recorded in the case-report form. (Rationale: Patients with kinase mutations can have very proliferative disease and the combination can induce differentiation in patients as part of response)
• Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted. Patients with a known history of CNS disease must have been treated with CNS directed therapy, have at least 2 consecutive LPs with no evidence of CNS leukemia, and must be clinically stable for at least 4 weeks prior to enrollment and have no ongoing neurological symptoms that in the opinion of the treating physician are related to the CNS disease

You may not qualify if:

• Patients with known allergy or hypersensitivity to ASTX727(Inqovi), ASTX029 or any of their components.
• Patients with known allergy or hypersensitivity to ASTX727(Inqovi), ASTX029 or any of their components.
• Patients with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which could compromise participation in the study.
• Patients on active antineoplastic or radiation therapy for a concurrent malignancy at the time of screening. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed.
• Prior organ transplantation including allogenic stem-cell transplantation within 3 months prior to planned enrollment, active graft versus host disease (GVHD) \>Grade 1 or requiring transplant-related immunosuppression with the exception of low dose cyclosporine and tacrolimus.
• Prior treatment with an ERK inhibitor.
• History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:
• A) Presence of predisposing factors to RVO or CSR (eg, uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus) or b) Visible retinal pathology as assessed by ophthalmic examination at screening that is considered a risk factor for RVO or CSR such as:
• Evidence of optic disc cupping or
• Evidence of new visual field defects on automated perimetry or
• Intraocular pressure \>21mmHg as measured by tonography.
• Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia.
• Patients with a known HIV infection that is not well controlled (i.e. any detectable circulating viral load) at the time of enrollment. No additional screening for HIV infection is needed.
• Patients with known positive hepatitis B or C infection by serology, with the exception of those with an undetectable viral load within 3 months (Hepatitis B or C testing is not required prior to study entry). Subjects with serologic evidence of prior vaccination to HBV \[i.e., HBs Ag-, and anti-HBs+\] may participate.
• Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Gautam Borthakur, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: November 2, 2023
• Study Start: February 8, 2024
• Primary Completion: March 6, 2025
• Study Completion: March 6, 2025
• Last Updated: March 12, 2025

Record last verified: 2025-03