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

Edgewood Oncology

Status and phase: Enrolling; Phase 1

Conditions: Myelodysplastic Syndrome; Acute Myeloid Leukemia

Treatments: Drug: Azacitidine; Drug: BTX-A51

Study type: Interventional

Funder types: Industry

Identifiers

NCT04243785

BTX-A51-001

Details and patient eligibility

About

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).

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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80 participants in 3 patient groups

Part 1a (Monotherapy Cohort Escalation)

Experimental group

Description:

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.

Treatment:

Drug: BTX-A51

Part 1b (Monotherapy Cohort Expansion)

Experimental group

Description:

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.

Treatment:

Drug: BTX-A51

Part 1c (Azacitidine Combination Dose Escalation)

Experimental group

Description:

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.

Treatment:

Drug: BTX-A51

Drug: Azacitidine