Recruiting
Phase 1
A Study of BTX-A51 in People With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Condition(s) studied
Acute Myeloid LeukemiaMyelodysplastic Syndrome
Investigational drug(s) / intervention(s)
BTX-A51Azacitidine
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.
Study 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).
Eligibility
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
Primary outcome measure(s)
- Incidence of dose-limiting toxicities (DLTs) — Up to a total of eight 28-day cycles (approximately 224 days)
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.
- Number of participants with non-serious AEs and serious AEs (SAEs) — Up to a total of eight 28-day cycles (approximately 224 days)
The severity/intensity of AEs will be graded based upon the participant's symptoms according to the NCI CTCAE Version 5.0
- Number of participants with laboratory abnormalities and/or AEs — Up to a total of eight 28-day cycles (approximately 224 days)
Number of participants with potentially clinically significant laboratory values; toxicity will be graded and reported according to the NCI CTCAE Version 5.0
- Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs — Up to a total of eight 28-day cycles (approximately 224 days)
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
- Number of participants with echocardiogram (ECHO) abnormalities and/or AEs — Up to a total of eight 28-day cycles (approximately 224 days)
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)
- Number of participants with vital sign abnormalities and/or AEs — Up to a total of eight 28-day cycles (approximately 224 days)
Number of participants with potentially clinically significant vital sign values; toxicity will be graded and reported according to the NCI CTCAE Version 5.0
- Number of participants with physical examination abnormalities and/or AEs — Up to a total of eight 28-day cycles (approximately 224 days)
Number of participants with potentially clinically significant physical examination findings; toxicity will be graded and reported according to the NCI CTCAE Version 5.0
- Maximum tolerated dose (MTD) — Up to 28 days (one cycle) for each dosing cohort in Phase 1a
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.
- Recommended Phase 2 dose (RP2D) — Up to 28 days (one cycle) for each dosing cohort in Phase 1b
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)
Trial sites (3)
| Facility | City | Region | Status |
|---|
| City of Hope National Medical Center |
Duarte |
California |
Recruiting |
| Memorial Sloan-Kettering Cancer Center |
New York |
New York |
Recruiting |
| The University of Texas MD Anderson Cancer Center |
Houston |
Texas |
Recruiting |