ASTX727 and FT-2102 in Treating IDH1-Mutated Recurrent/Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

NCT04013880 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: VICC HEM 18165NCI-2019-04103
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase Ib/II trial studies the side effects and best dose of FT-2102 when given together with ASTX727 in treating patients with IDH1-mutated myelodysplastic syndrome or acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). ASTX727 is an oral deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor. DNA methylation is necessary for cell differentiation and development. Changes to the methylation profile can lead to DNA instability which can cause diseases like cancer. DNMT inhibitors target and inhibit these changes. FT-2102 is an isocitrate dehydrogenase 1 (IDH1) inhibitor. IDH1 is a type of protein involved in metabolism, or the process of providing the body's cells with energy. FT-2102 may stop the abnormal IDH1 protein and may reduce 2-HG levels in diseased cells to levels found in normal cells. Giving ASTX727 and FT-2102 may work better in treating patients with myelodysplastic syndrome or acute myeloid leukemia compared to ASTX727 and FT-2102 alone.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Recurrent Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (Phase Ib)

  Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  Up to 30 days

• Response rate (Phase II)

  calculated for each cohort, together with 95% confidence intervals based on exact binomial distributions.

  Approximately 12 months

Secondary Outcomes (7)

• To confirm the phase II recommended dosing level (1b)

  At 28 days

• Pharmacokinetics parameters (1b)

  Approximately 12 months

• Reduction of bone marrow blasts (phase II)

  Approximately 12 months

• Overall survival (Phase II)

  Up to 2 years

• Event-Free Survival (Phase II)

  Up to 2 years

Study Arms (1)

Treatment (ASTX727, FT-2102)

EXPERIMENTAL

Patients receive CDA inhibitor E7727/decitabine combination agent ASTX727 PO QD on days 1-5 and IDH-1 inhibitor FT-2102 PO QD or BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: CDA Inhibitor E7727/Decitabine Combination Agent ASTX727; Drug: IDH-1 Inhibitor FT-2102

Interventions

CDA Inhibitor E7727/Decitabine Combination Agent ASTX727 DRUG

Given by mouth

Also known as: ASTX727

Treatment (ASTX727, FT-2102)

IDH-1 Inhibitor FT-2102 DRUG

Given by mouth

Also known as: FT 2102, FT-2102, IDH1-R132 Inhibitor FT-2102

Treatment (ASTX727, FT-2102)

Eligibility Criteria

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

You may qualify if:

• Must voluntarily sign an informed consent document (ICF)
• Morphologically confirmed diagnosis of MDS (inclusive of MDS/MPN) or AML in accordance with World Health Organization (WHO) diagnostic criteria
• Phase Ib: Subjects may have
• Relapsed/refractory AML or MDS or
• Treatment naive AML
• Phase II Expansion: Subjects may have
• Relapsed/refractory AML or MDS or
• Treatment naive AML or
• Treatment naive MDS
• For patients with MDS, must have a Revised International Prognostics Scoring System (IPSS-R) risk category of intermediate, high, or very high
• Confirmed IDH1 R132 mutation
• A bone marrow biopsy must be performed and tissue collected for entrance to the trial
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Life expectancy of at least 3 months in the assessment of the investigator
• Recovery from the non-hematologic toxic effects of prior treatment to grade =\< 1, or baseline value according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03 classification (excluding infertility, alopecia, or grade 1 neuropathy)

You may not qualify if:

• Treatment naive patients who are suitable for and willing to receive intensive induction chemotherapy
• Patients with active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible
• Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol
• Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection (hepatitis B carriers with normal liver function test \[LFT\]s and undetectable viral loads are allowed)
• Women who are pregnant or nursing
• Organ transplant recipients other than bone marrow transplant
• Autologous hematologic stem cell transplant within 3 months of study entry. Allogeneic hematologic stem cell transplant within 6 months. Grade II, or greater, active graft-versus- host disease
• Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of FT-2102/ASTX727. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of FT-2102/ASTX727 is required
• Any major surgery, chemotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed \>= 2 weeks); concurrent hydroxyurea is allowed if less than or equal to 2 grams daily
• Ongoing immunosuppressive therapy including systemic corticosteroids (prednisone or equivalent =\< 20 mg daily allowed as clinically warranted). Patients are allowed to use topical or inhaled corticosteroids
• Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.
• Patients unable to swallow oral medications, or patients with gastrointestinal conditions (e.g., malabsorption, resection, etc.) deemed by the Investigator to jeopardize intestinal absorption
• Patients receiving intrathecal chemotherapy for active central nervous system (CNS) disease
• Patients who have exhibited allergic reactions to a previously administered IDH1 inhibitor
• Patients with acute promyelocytic leukemia (APL)

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• Astex Pharmaceuticals, Inc.: collaborator
• Forma Therapeutics, Inc.: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

decitabine and cedazuridine drug combination; olutasidenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Paul Ferrell, MD

  Vanderbilt Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 5, 2019
• First Posted: July 10, 2019
• Study Start: August 27, 2019
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2022
• Last Updated: July 7, 2020

Record last verified: 2020-07