Recruiting
Phase 1

BTX-A51

Sponsor:

Edgewood Oncology Inc.

Code:

NCT04243785

Conditions

Acute Myeloid Leukemia

Myelodysplastic Syndrome

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BTX-A51

Azacitidine

Study Details

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

Study ID

NCT04243785

Start date

Jan 6, 2020

Status verified date

Feb, 2024

Completion date

Mar, 2027

Anticipated

Primary completion date

Mar, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Study Design

Enrollment

80 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1a (Monotherapy Cohort Escalation)

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.

experimental: Part 1b (Monotherapy Cohort Expansion)

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.

experimental: Part 1c (Azacitidine Combination Dose Escalation)

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.

Interventions

BTX-A51

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

Azacitidine

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

Primary outcome measure

  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to a total of eight 28-day cycles (approximately 224 days) ]
  • Number of participants with non-serious AEs and serious AEs (SAEs) [ Time Frame: Up to a total of eight 28-day cycles (approximately 224 days) ]
  • Number of participants with laboratory abnormalities and/or AEs [ Time Frame: Up to a total of eight 28-day cycles (approximately 224 days) ]
  • Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs [ Time Frame: Up to a total of eight 28-day cycles (approximately 224 days) ]
  • Number of participants with echocardiogram (ECHO) abnormalities and/or AEs [ Time Frame: Up to a total of eight 28-day cycles (approximately 224 days) ]
  • Number of participants with vital sign abnormalities and/or AEs [ Time Frame: Up to a total of eight 28-day cycles (approximately 224 days) ]
  • Number of participants with physical examination abnormalities and/or AEs [ Time Frame: Up to a total of eight 28-day cycles (approximately 224 days) ]
  • Maximum tolerated dose (MTD) [ Time Frame: Up to 28 days (one cycle) for each dosing cohort in Phase 1a ]
  • Recommended Phase 2 dose (RP2D) [ Time Frame: Up to 28 days (one cycle) for each dosing cohort in Phase 1b ]

Central Contacts and Locations

Central contacts

Zung Thai, MD

415-225-9338zung@edgewoodonc.com

Edgar Bautista

edgar@edgewoodonc.com

Locations

City of Hope National Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Brian Ball, MD

626-218-4784brball@coh.org

Memorial Sloan-Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Eytan Stein, MD

646-608-3749SteinE@mskcc.org

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Gautam Borthakur, MD

713-563-1586Gborthak@mdanderson.org

More Information

Sponsor

Edgewood Oncology Inc.

Last update posted

Mar 20, 2024

Last verified

Feb, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Edgewood Oncology Inc. on 2024-03-20.