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Acute Myeloid LeukemiaPhase 1/2NCT04013880

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

A Phase 1/2 study testing CDA Inhibitor E7727/Decitabine Combination Agent ASTX727 and IDH-1 Inhibitor FT-2102 in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Vanderbilt-Ingram Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CDA Inhibitor E7727/Decitabine Combination Agent ASTX727 and IDH-1 Inhibitor FT-2102
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
27 Aug 2019to 31 Mar 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Must have adequate hepatic and renal function as demonstrated by the following:
  • ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN); Direct bilirubin ≤ 1.5 x ULN(or ≤ 2x ULN if due to Gilbert's disease); Serum creatinine of 1.5 x ULN or creatinine clearance of > 50 mL/min (whichever is lower)
  • Baseline Fridericia's correction formula (QTcF) =< 450 msec (average of the QTcF values of screening triplicate electrocardiography [ECG]swith approximately two-minute intervals ) except for those patients with a bundle branch block (BBB)
  • For fertile men and women, agreement to use effective contraceptive methods for the duration of study participation and 90 days after the last dose of study medication

Who cannot join

  • 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
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  • 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)

About this study

Official title: A Phase IB/II Study to Evaluate the Safety, Tolerability, and Efficacy of ASTX727 and FT-2102 in IDH1-Mutated Myelodysplastic Syndrome or Acute Myeloid Leukemia

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.

Read the detailed description

PRIMARY OBJECTIVES:

  • To evaluate the safety of IDH-1 inhibitor FT-2102 (FT-2102) in combination with CDA inhibitor E7727/decitabine combination agent ASTX727 (ASTX727) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients with IDH1 R132 mutations. (Phase Ib)
  • To evaluate the response rate (overall response rate [ORR], complete response [CR], complete remission with partial hematologic recovery (CRh), complete remission with incomplete blood count recovery [CRi], morphologic leukemia-free state [MLFS], partial response [PR]) of the combination of ASTX727 and the IDH1-inhibitor, FT-2102 in subjects with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with IDH1 R132 mutations. (Phase II)

SECONDARY OBJECTIVES:

  • To confirm the phase II recommended dosing level of FT-2102 and ASTX727 in combination. (Phase Ib)
  • To determine the pharmacokinetics of FT-2102 and ASTX727 in combination. (Phase Ib)
  • To determine the reduction of bone marrow blasts. (Phase II)
  • To determine the overall survival and event-free survival. (Phase II)
  • To determine the levels of 2-HG in the blood and blood cells after treatment. (Phase II)
  • To determine the relationship of 2-HG reduction to clinical response. (Phase II)

OUTLINE: This is a phase Ib, dose-escalation of IDH-1 inhibitor FT-2102 followed by a phase II study.

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

After completion of study treatment, patients are followed up at 30 days, every 3 months for 12 months, and then periodically for up to 5 years.

Being tested
CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, IDH-1 Inhibitor FT-2102
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CDA Inhibitor E7727/Decitabine Combination Agent ASTX727Drug

    Also called ASTX727

    Given by mouth

  • IDH-1 Inhibitor FT-2102Drug

    Also called FT 2102, FT-2102, IDH1-R132 Inhibitor FT-2102

    Given by mouth

Study groups in NCT04013880
Study groupRoleWhat they receive
Treatment (ASTX727, FT-2102)ExperimentalPatients 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.
Receives: Drug: CDA Inhibitor E7727/Decitabine Combination Agent ASTX727; Drug: IDH-1 Inhibitor FT-2102

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events (Phase Ib)

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

    Measured: Up to 30 days

  2. Response rate (Phase II)

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

    Measured: Approximately 12 months

Secondary outcomes (7)

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

    Measured: At 28 days

  2. Pharmacokinetics parameters (1b)

    analysis of plasma concentrations during the dose escalation phase of the study

    Measured: Approximately 12 months

  3. Reduction of bone marrow blasts (phase II)

    Measured: Approximately 12 months

  4. Overall survival (Phase II)

    Time from randomization to death due to any cause

    Measured: Up to 2 years

  5. Event-Free Survival (Phase II)

    Time from start of treatment to event that treatment was intended to prevent or delay

    Measured: Up to 2 years

  6. Measure change in levels of 2-HG in the blood and blood cells after treatment (Phase II)

    Measured: Up to 12 months

  7. Compare 2-HG change to clinical response (Phase II)

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jul 2019
  2. Study start27 Aug 2019
  3. Primary completion31 Mar 2021 (estimated)
  4. Study completion31 Mar 2022 (estimated)

Why it stopped: Loss of funding

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04013880
Sponsor's protocol ID
VICC HEM 18165
Other IDs
NCI-2019-04103
Status last verified
Jul 2020
First submitted
5 Jul 2019
Last updated
7 Jul 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CDA Inhibitor E7727/Decitabine Combination Agent ASTX727 and IDH-1 Inhibitor FT-2102 in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Vanderbilt-Ingram Cancer Center.

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 19 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: withdrawn, as of the sponsor's last update on 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (Phase Ib) (time frame: Up to 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04013880.

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 7 Jul 2020.

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