NCT04243785 · Edgewood Oncology Inc.
A Study of BTX-A51 in People With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
What this study is about
This is an where both patients and doctors know the treatment given, gradually increasing doses study to evaluate the safety, toxicity, and how the drug moves through the body (PK) as well as preliminary effectiveness 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.
View original scientific description
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).
Interventions
DRUG
BTX-A51
Orally administered capsules available in strengths of 0.5 mg, 1.0 mg, 2.0 mg and 7 mg.
DRUG
Azacitidine
Azacitidine will be administered IV or SC 75 mg/m2 QD on Days 1-7 of each 28-day cycle.
Primary outcome measures
Incidence of dose-limiting toxicities (DLTs)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- Duarte, California
- New York, New York
- Houston, Texas
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 20, 2024 · Source of record for eligibility and locations