A Study of BTX-A51 in People With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT04243785 | Recruiting Phase 1 FDA Drug

• 1 other identifier: BTX-A51-001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, dose escalation study to evaluate the safety, toxicity, and pharmacokinetics (PK) as well as preliminary efficacy of BTX-A51 capsules in participants with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). The study will be done in three parts. Part 1a (Monotherapy Dose Escalation) of this study is designed to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of orally administered BTX-A51 in up to 35 participants who are evaluable for toxicity. Once the MTD is determined, it is planned that an additional 15 participants will be enrolled in Part 1b (Monotherapy Cohort Expansion) of this study for additional experience with safety and efficacy, and to determine the recommended Phase 2 dose (RP2D) which may or may not be different from the MTD. After determination of MTD and RP2D from Part 1a, Part 1c (Azacitidine Combination Dose Escalation) will enroll up to 30 participants. Continued treatment will be available under this study protocol for up to eight 28-day cycles (Continued Treatment Phase) if the Investigator judges the benefit outweighs the risk. Once BTX-A51 treatment has completed, participants will be contacted by telephone every 3 months for up to 2 years after their last treatment for survival status and anticancer therapy (Overall Survival Follow-up).

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (9)

• Incidence of dose-limiting toxicities (DLTs)

  A DLT is defined as a severe or clinically significant adverse event (AE) or abnormal laboratory value (Grade 3 or greater, unless otherwise specified) starting with the first dose on Cycle 1 Day 1, unless it is clearly related to disease progression, intercurrent illness, preexisting condition, or concomitant medications. DLTs are based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  Up to a total of eight 28-day cycles (approximately 224 days)

• Number of participants with non-serious AEs and serious AEs (SAEs)

  The severity/intensity of AEs will be graded based upon the participant's symptoms according to the NCI CTCAE Version 5.0

  Up to a total of eight 28-day cycles (approximately 224 days)

• Number of participants with laboratory abnormalities and/or AEs

  Number of participants with potentially clinically significant laboratory values; toxicity will be graded and reported according to the NCI CTCAE Version 5.0

  Up to a total of eight 28-day cycles (approximately 224 days)

• Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs

  Number of participants with potentially clinically significant 12-lead ECG findings; toxicity will be graded and reported according to the NCI CTCAE Version 5.0

  Up to a total of eight 28-day cycles (approximately 224 days)

• Number of participants with echocardiogram (ECHO) abnormalities and/or AEs

  Number of participants with potentially clinically significant ECHO abnormalities and/or AEs, such as elevated or abnormal left ventricular ejection fraction (LVEF) or abnormal Global Longitudinal Strain (GLS)

  Up to a total of eight 28-day cycles (approximately 224 days)

• Number of participants with vital sign abnormalities and/or AEs

  Number of participants with potentially clinically significant vital sign values; toxicity will be graded and reported according to the NCI CTCAE Version 5.0

  Up to a total of eight 28-day cycles (approximately 224 days)

• Number of participants with physical examination abnormalities and/or AEs

  Number of participants with potentially clinically significant physical examination findings; toxicity will be graded and reported according to the NCI CTCAE Version 5.0

  Up to a total of eight 28-day cycles (approximately 224 days)

• Maximum tolerated dose (MTD)

  The DLTs are to be evaluated for determination of the MTD. The MTD will be the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate of 0.3. If there are ties, the higher dose level when the isotonic estimate is lower than the target toxicity rate will be identified and the lower dose level selected when the isotonic estimate is greater than or equal to the target toxicity rate.

  Up to 28 days (one cycle) for each dosing cohort in Phase 1a

• Recommended Phase 2 dose (RP2D)

  The DLTs are to be evaluated based on cumulative safety/PK data in participants treated in Phase 1b for determination of the RP2D (which may or may not differ from the MTD)

  Up to 28 days (one cycle) for each dosing cohort in Phase 1b

Secondary Outcomes (17)

• Complete remission (CR) for participants with acute myeloid leukemia (AML)

  Up to a total of eight 28-day cycles (approximately 224 days)

• Complete remission with incomplete blood count recovery (CRi) for participants with AML

  Up to a total of eight 28-day cycles (approximately 224 days)

• Morphologic leukemia-free state (MLFS) for participants with AML

  Up to a total of eight 28-day cycles (approximately 224 days)

• Partial remission (PR) for participants with AML

  Up to a total of eight 28-day cycles (approximately 224 days)

• Complete remission (CR) for participants with high-risk myelodysplastic syndrome (MDS)

  Up to a total of eight 28-day cycles (approximately 224 days)

Study Arms (3)

Part 1a (Monotherapy Cohort Escalation)

EXPERIMENTAL

Dosing in this phase of the study consists of the first cycle of therapy (i.e., 28 days consisting of 3 weeks of treatment followed by 1 week with no study drug). The BTX-A51 starting dose for Cohort 1 is 1 mg, to be given 5 days per week (maximum weekly dose of 5 mg). Beginning with Cohort 2, doses are intended to be administered 3 days per week. Barring dose-limiting toxicity (DLT), sequential dose escalation of BTX-A51 is planned with up to a total of eight dose levels to a maximum of 21 mg (63 mg/week); on the basis of these an MTD will be identified. The numbers of participants and actual doses administered will be determined using a Bayesian optimal interval (BOIN) design to determine the DLTs and MTD of BTX-A51.

Drug: BTX-A51

Part 1b (Monotherapy Cohort Expansion)

EXPERIMENTAL

Dosing in this phase of the study consists of the first cycle of therapy (i.e., 28 days consisting of 3 weeks of treatment followed by 1 week with no study drug). Part 1b will continue at the MTD or the highest dose achieved in Phase 1a.

Drug: BTX-A51

Part 1c (Azacitidine Combination Dose Escalation)

EXPERIMENTAL

After determination of MTD and RP2D from Part 1a, combination dose escalation in Part 1c may begin. Patients with AML will receive BTX-A51 combined with azacitidine in escalating BTX-A51 dose cohorts. Dosing in this stage of the study consists of the first cycle of therapy (i.e., 28 days). The starting dose of BTX-A51 will be RP2D. Part 1c will follow a BOIN design as described for Part 1a. The numbers of patients and actual doses administered will be determined in response to DLTs a. There will be at least 3 patients per cohort.

Drug: BTX-A51; Drug: Azacitidine

Interventions

BTX-A51 DRUG

Orally administered capsules available in strengths of 0.5 mg, 1.0 mg, 2.0 mg and 7 mg.

Part 1a (Monotherapy Cohort Escalation); Part 1b (Monotherapy Cohort Expansion); Part 1c (Azacitidine Combination Dose Escalation)

Azacitidine DRUG

Azacitidine will be administered IV or SC 75 mg/m2 QD on Days 1-7 of each 28-day cycle.

Part 1c (Azacitidine Combination Dose Escalation)

Eligibility Criteria

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

You may qualify if:

• Demonstration of understanding and voluntarily signing of an informed consent form
• Age ≥ 18 years
• Diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) according to the World Health Organization classification and, with respect to MDS, that is high risk; participants must have refractory or relapsed disease and be ineligible for or have exhausted standard therapeutic options that would otherwise be likely to provide clinical benefit
• Eastern Cooperative Oncology Group performance status ≤ 2 and life expectancy of ≥ 6 weeks
• Adequate organ function (Grade 1 serum creatinine; Grade 1 total bilirubin; aspartate aminotransferase and/or alanine transaminase ≤ 2 × ULN)
• Females of childbearing age must not be pregnant at time of Screening/beginning of treatment and agree to either abstain from sexual intercourse or use highly effective methods of contraception (for up to 3 months after last dose of study drug)
• Males sexually active with a woman of childbearing age must agree to use barrier method of birth control during and after the study (up to 3 months after last dose of study drug)

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia
• White blood cell count \> 20 x 10\^9/L
• Receipt of cancer chemotherapy (other than hydroxyurea) within 2 weeks prior to the start of study drug
• In participants who have undergone autologous or allogeneic stem cell transplantation: transplantation within the 3 months prior to Screening; active graft-versus-host disease requiring anything other than topical corticosteroids and budesonide; treatment with systemic immunosuppressive medications including high-dose steroids (≥ 20 mg prednisolone or equivalent per day), or calcineurin inhibitors (e.g., cyclosporine, tacrolimus) for at least 1 week prior to Screening, and sirolimus, mycophenylate mofetil, azathioprine, or ruxolitinib for at least 2 weeks prior to Screening
• Immediate life-threatening severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
• Persistent toxicities from prior treatment of Grade 2 or higher
• Active uncontrolled systemic fungal, bacterial, mycobacterial, or viral infection
• Clinically significant cardiac disease
• Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
• Any other concurrent medical condition or disease that is likely to interfere with study procedures or results, or that, in the opinion of the Investigator, would constitute a hazard for participating in this study
• If female, pregnant or breastfeeding

Sponsors & Collaborators

• Edgewood Oncology Inc.: lead

Study Sites (3)

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Zung Thai, MD

  Edgewood Oncology Inc.

  STUDY DIRECTOR

Central Study Contacts

Zung Thai, MD

CONTACT

415-225-9338; zung@edgewoodonc.com

Edgar Bautista

CONTACT

edgar@edgewoodonc.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2020
• First Posted: January 28, 2020
• Study Start: January 6, 2020
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 20, 2024

Record last verified: 2024-02

Locations

US (3)