Study Augmenting TAK-659 Action in Relapsed/Refractory AML by Addition Ofthe Proteasome Inhibitor Ixazomib

NCT04079738 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: BTCRC-HEM17-092
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II study augmenting TAK-659 action in relapsed/refractory AML by addition of the proteasome inhibitor Ixazomib. Phase I of the study will determine the safety, tolerability, and maximum tolerated dose (MTD) of the combination of TAK-659 and Ixazomib. During the phase I, dose escalation will be conducted according to a standard 3+3 dose escalation schema, and up to 18 response-evaluable patients will be enrolled. Phase II of the study will evaluate the efficacy of the combination by measuring the overall response rate (ORR).

Conditions

AML; AML, Adult

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose(s) (RP2D)

  To determine the maximum tolerated dose (MTD) and recommended phase 2 dose(s) (RP2D) of the combination of TAK-659 and Ixazomib in patients with relapsed or refractory AML.

  At the end of Cycle 2(each cycle is 28 days)

• Overall Response Rate for Phase II Subjects.

  To evaluate preliminary efficacy of TAK-659 plus Ixazomib in relapsed or refractory AML as measured by overall response rate (ORR). Overall response rate (ORR) defined as CR, CRp, CRi, and PR per Revised Recommendations of the International Working Group (IWG) for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia.

  Overall Response rate is assessed at the end of 4 cycles ; 4 months.

Secondary Outcomes (5)

• Duration of Response (DOR) for Phase II Subjects

  Up to two years after the date of the first documented response.

• Time to Progression (TTP) for Phase II Subjects

  time from first dose of study drug until tumor progression up to two years after the date of the first documented response.

• Overall Survival (OS) for Phase II Subjects

  time from the date of study entry up to two years.

• Frequency of Grade 3 and Higher Adverse Events for Phase II Subjects

  From date of first dose until 30 days after the last treatment up to 1 year.

• Mortality Rate at 3 and 6 Months for Phase II Subjects

  From start of treatment up to 2 years or until death.

Study Arms (2)

Phase I:TAK-659 + Ixazomib

EXPERIMENTAL

Phase I: TAK-659 (Days 1-15) + Ixazomib dose escalation (Days 1, 8, 15)

Drug: TAK-659; Drug: Ixazomib

Phase II:TAK-659 + Ixazomib

EXPERIMENTAL

Phase II: TAK-659 at MTD (Days 1-15) + Ixazomib at MTD (Days 1, 8, 15)

Drug: TAK-659; Drug: Ixazomib

Interventions

TAK-659 DRUG

TAK-659

Phase I:TAK-659 + Ixazomib; Phase II:TAK-659 + Ixazomib

Ixazomib DRUG

Ixazomib

Phase I:TAK-659 + Ixazomib; Phase II:TAK-659 + Ixazomib

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Male or female patients 18 years or older at the time of consent.
• Patients must have a diagnosis of primary or secondary AML with relapsed or refractory disease (WHO update 2016, \[34\]) other than acute promyelocytic leukemia, or complex karyotype or monosomy 7 (or containing monosomy 7) for whom no standard therapies are anticipated to result in a durable remission according to the clinical judgment of the treating physician, or in a patient who refuses standard therapies.
• Must have submitted for Next Generation Sequencing (NGS) testing by: 1) (preferred) having submitted a tumor sample for commercial myeloid NGS from Foundation One, Mayo, Tempus, Quest, ARUP or an institutional CLIA-certified laboratory and/or 2) obtaining a bone marrow aspirate during screening for submission to Foundation One, Mayo, Tempus, Quest, ARUP or an institutional CLIA-certified laboratory and ordered as standard of care. If bone marrow aspiration has failed, a peripheral blood sample with circulating blasts may be substituted. Screening reports on tumor cytogenetics and/or mutation assays (eg, FLT-3, and NGS) performed as part of the standard of care will be recorded in the study database or obtained at the time of screening if not previously available.
• Patient's disease must be characterized for the presence/absence of Flt3ITD/TKD mutation from an FDA-approved vendor (ex. LabPMM).
• In addition, patients for the phase 2 portion of the study must meet the following:
• Patients, if relapsed/ refractory, must have exposure to no more than 2 prior chemotherapy regimens. Re-induction with the same regimen or stem cell transplant will not be considered a separate regimen.
• Patients must not have prior exposure to any investigational Flt3 inhibitors (midostaurin or gilteritinib are allowed)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy of greater than 3 months as determined by the treating physician.
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, or
• Agree to practice true abstinence, when is in line with the preferred and usual lifestyle of the subject. Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)

You may not qualify if:

• Clinically active central nervous system leukemia.
• Female patients who are lactating and breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Female patients who have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
• Any serious medical or psychiatric illness, including drug or alcohol abuse, that could, in the investigator's opinion, potentially jeopardize the safety of the patient or interfere with the objectives of the study.
• Prior treatment with investigational agents ≤ 21 days or ≤ 5 half-lives (whichever is shorter) before the first dose of study treatment. A minimum of 10 days should elapse from prior investigational therapy to initiating protocol therapy.
• Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the NCI CTCAE (v5).
• Receipt of HSCT within 60 days of the first dose of TAK-659/Ixazomib; clinically significant graft-versus-host disease (GVHD) requiring ongoing immunosuppressive therapy post HSCT at the time of screening (use of topical steroids for ongoing skin GVHD is permitted).
• Active, systemic infection requiring intravenous (IV) antibiotic, antifungal, or antiviral therapy or other serious infection within 10 days before the first dose of study drug.
• Major surgery within 14 days before the first dose of study drug and have not recovered fully from any complications from surgery.
• Radiotherapy less than 2 weeks before the first dose of study treatment or have not recovered from acute toxic effects from radiotherapy.
• Known human immunodeficiency virus (HIV) positive.
• Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection (testing not required).
• Any of the following cardiovascular conditions:
• Acute myocardial infarction within 6 months before starting study drug.
• Current or history of New York Heart Association Class III or IV heart failure (see Study Procedures Manual \[SPM\]).

Sponsors & Collaborators

• H Scott Boswell: lead
• Takeda: collaborator

Study Sites (1)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

TAK-659; ixazomib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Annesha Majumdar
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• H Scott Boswell, MD

  Indiana University Melvin and Bren Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Medicine, Division of Hematology/Oncology, IU School of Medicine

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 6, 2019
• Study Start: September 20, 2019
• Primary Completion: September 22, 2021
• Study Completion: February 23, 2022
• Last Updated: September 13, 2023
• Results First Posted: September 13, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)