Acute Myeloid LeukemiaPhase 1NCT04243785
A Study of BTX-A51 in People With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
A Phase 1 study testing BTX-A51 and Azacitidine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Edgewood Oncology Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- What is being tested?
- BTX-A51 and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 3 sitesUnited States
- Study dates
- 6 Jan 2020to Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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 locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Edgar Bautista contact
United States3 sites, 3 recruiting
- Recruiting
City of Hope National Medical Center
Duarte, California, 91010
Brian Ball, MD, 626-218-4784, brball@coh.org
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Gautam Borthakur, MD, 713-563-1586, Gborthak@mdanderson.org
- Recruiting
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Eytan Stein, MD, 646-608-3749, SteinE@mskcc.org
About this study
Official title: A First-In-Human, Open-Label, Escalating Multiple-Dose Study to Evaluate the Safety, Toxicity, and Pharmacokinetics of BTX-A51 Alone and in Combination With Azacitidine in Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
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.
Read more
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
- Being tested
- BTX-A51, Azacitidine
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BTX-A51Drug
Orally administered capsules available in strengths of 0.5 mg, 1.0 mg, 2.0 mg and 7 mg.
AzacitidineDrug
Azacitidine will be administered IV or SC 75 mg/m2 QD on Days 1-7 of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: BTX-A51; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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.
Measured: 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)
Measured: 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)
CR is defined as free of all symptoms related to leukemia and with an absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (1000/µL), platelet count ≥ 100 × 10^9/L (100,000/µL), and normal bone marrow (BM) with < 5 percent blasts; absence of circulating blasts and blasts with Auer rods
Measured: Up to a total of eight 28-day cycles (approximately 224 days)
Complete remission with incomplete blood count recovery (CRi) for participants with AML
CRi is defined as all CR criteria except for residual neutropenia (ANC < 1.0 × 10^9/L [1000/µL]) or thrombocytopenia (platelet count < 100 × 10^9/L [100,000/µL])
Measured: Up to a total of eight 28-day cycles (approximately 224 days)
Morphologic leukemia-free state (MLFS) for participants with AML
MLFS is defined as BM blasts < 5 percent; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. Marrow should not barely be "aplastic;" at least 200 cells should be enumerated or cellularity should be at least 10 percent.
Measured: Up to a total of eight 28-day cycles (approximately 224 days)
Partial remission (PR) for participants with AML
PR is defined as all hematologic criteria of CR; decrease of BM blast percentage to 5 - 25 percent; and decrease of pretreatment BM blast percentage by at least 50 percent
Measured: Up to a total of eight 28-day cycles (approximately 224 days)
Complete remission (CR) for participants with high-risk myelodysplastic syndrome (MDS)
CR is defined as free of all symptoms related to leukemia and with an ANC ≥ 1.0 × 10^9/L, platelet count ≥ 100 × 10^9/L, BM ≤ 5 percent myeloblasts, with normal maturation of all cell lines, hemoglobin ≥ 11 g/dL, and no blasts in peripheral blood (PB)
Measured: Up to a total of eight 28-day cycles (approximately 224 days)
Partial remission (PR) for participants with high-risk MDS
PR is defined as all CR criteria with ≥ 50 percent decrease in BM blasts over pre-treatment (but still > 5 percent)
Measured: Up to a total of eight 28-day cycles (approximately 224 days)
Hematologic improvement (HI) for participants with high-risk MDS
The International Working Group criteria for HI defining specific responses of cytopenias in the three hematopoietic lineages: erythroid (HI-E), platelet (HI-P), and neutrophil (HI-N)
Measured: Up to a total of eight 28-day cycles (approximately 224 days)
Overall survival and event-free survival in participants with AML or high-risk MDS
Follow-up will occur by telephone contact once every 3 months for assessment of survival status and bone marrow transplant (BMT) conditioning or other new antineoplastic therapies since discontinuation of study drug; the cause of death will be documented. Disease assessment will be collected for participants who discontinue study medication due to any reason other than progression or death. If a participant has not progressed or died, progression-free survival is censored at the date of last follow up. The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier.
Measured: Up to 2 years after participant's last dose of BTX-A51 or upon death, whichever occurs first
PK parameter: Maximum observed plasma concentration (Cmax)
Maximum observed plasma drug concentration after the first dose
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Time of maximum plasma concentration (Tmax)
Time to reach Cmax
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Plasma CmaxD5
Maximum observed plasma drug concentration after the dose on Day 5
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Plasma TmaxD5
Time to reach CmaxD5
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: C0
Pre-dose concentrations in PK blood samples on dosing days
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: AUC0-24
Area under the curve from time 0 to 24 hours after the first dose
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: AUC0-24D5
AUC from time 0 to 24 hours after the dose on Day 5
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Terminal elimination rate constant (Kel)
Calculated by linear least-squares regression analysis from a semi-log plot of the plasma concentration versus time curve after the Day 5 dose
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Terminal elimination phase half-life (t1/2)
Estimated after the Day 5 dose, calculated as 0.693/Kel
Measured: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2020
- Study start6 Jan 2020
- Primary completionMar 2026 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Edgewood Oncology Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zung Thai, MD, Study director, Edgewood Oncology Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04243785
- Sponsor's protocol ID
- BTX-A51-001
- Status last verified
- Feb 2024
- First submitted
- 24 Jan 2020
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-In-Human, Open-Label, Escalating Multiple-Dose Study to Evaluate the Safety, Toxicity, and Pharmacokinetics of BTX-A51 Alone and in Combination With Azacitidine in Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT04243785
- Acronym / sponsor ID
- BTX-A51-001
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Edgewood Oncology Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Jan 2020 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 28 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1a (Monotherapy Cohort Escalation) | Experimental | Drug: BTX-A51Dosing 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. |
| Part 1b (Monotherapy Cohort Expansion) | Experimental | Drug: BTX-A51Dosing 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. |
| Part 1c (Azacitidine Combination Dose Escalation) | Experimental | Drug: BTX-A51, Drug: AzacitidineAfter 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BTX-A51Orally administered capsules available in strengths of 0.5 mg, 1.0 mg, 2.0 mg and 7 mg. | Drug | Part 1a (Monotherapy Cohort Escalation), Part 1b (Monotherapy Cohort Expansion), Part 1c (Azacitidine Combination Dose Escalation) |
| AzacitidineAzacitidine will be administered IV or SC 75 mg/m2 QD on Days 1-7 of each 28-day cycle. | Drug | Part 1c (Azacitidine Combination Dose Escalation) |
Primary outcome
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)
17 secondary outcomes
Complete remission (CR) for participants with acute myeloid leukemia (AML)
Time frame: Up to a total of eight 28-day cycles (approximately 224 days)
Complete remission with incomplete blood count recovery (CRi) for participants with AML
Time frame: Up to a total of eight 28-day cycles (approximately 224 days)
Morphologic leukemia-free state (MLFS) for participants with AML
Time frame: Up to a total of eight 28-day cycles (approximately 224 days)
Partial remission (PR) for participants with AML
Time frame: Up to a total of eight 28-day cycles (approximately 224 days)
Complete remission (CR) for participants with high-risk myelodysplastic syndrome (MDS)
Time frame: Up to a total of eight 28-day cycles (approximately 224 days)
Partial remission (PR) for participants with high-risk MDS
Time frame: Up to a total of eight 28-day cycles (approximately 224 days)
Hematologic improvement (HI) for participants with high-risk MDS
Time frame: Up to a total of eight 28-day cycles (approximately 224 days)
Overall survival and event-free survival in participants with AML or high-risk MDS
Time frame: Up to 2 years after participant's last dose of BTX-A51 or upon death, whichever occurs first
PK parameter: Maximum observed plasma concentration (Cmax)
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Time of maximum plasma concentration (Tmax)
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Plasma CmaxD5
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Plasma TmaxD5
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: C0
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: AUC0-24
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: AUC0-24D5
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Terminal elimination rate constant (Kel)
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
PK parameter: Terminal elimination phase half-life (t1/2)
Time frame: During Cycle 1 for each dosing cohort in Phase 1a on Days 1, 3, and 5 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose); Days 2, 4, 6, 7, 8; and Day 15 (pre-dose and approximately 1, 2, 3, 5, 8, and 12 hours post-dose)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Edgar Bautista contact
Zung Thai, MD study director
Edgewood Oncology Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BTX-A51 and Azacitidine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Edgewood Oncology Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zung Thai, MD (415-225-9338, zung@edgewoodonc.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (DLTs) (time frame: Up to a total of eight 28-day cycles (approximately 224 days)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.