A Study of Rebecsinib for Patients With Relapsed/Refractory Secondary Acute Myeloid Leukemia or High Risk Myelofibrosis
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAspera Biomedicines, Inc.
About this trial
The purpose of this study is to test the safest and most effective dose of a new investigational drug, rebecsinib. Participants in this study will have either Secondary Acute Myeloid Leukemia (sAML) that has either returned (relapsed) or not responded to treatment (refractory) or have higher risk Myelofibrosis (MF). Participants will receive a study drug infusion on Day 1, Day 4, Day 8 and Day 11 of each 28-day cycle for a total of 6 cycles.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Ability to understand and the willingness to sign a written informed consent.
Must have a refractory myeloid neoplasm (5th Edition WHO Classification of Tumors) consisting of secondary AML (sAML), which has evolved from antecedent MDS, MPN, MDS/MPN, or have higher-risk MF defined by DIPSS Plus or MIPSS70+ version 2.0, and excess bone marrow blasts (> 5%). Patients with sAML, defined as AML with an antecedent history of MDS or MPN or WHO AML with myelodysplasia related genetic changes or WHO AML with myelodysplasia related cytogenetic abnormalities. Must be ineligible for bone marrow transplantation at the time of enrollment and have relapsed or be refractory or intolerant to available therapies, such as anthracycline chemotherapy, epigenetic modifier therapy (azacytidine or decitabine) or venetoclax including any treatment that is active in specific mutations if relevant (e.g., FLT3 inhibitors for patients with FLT3 mutations). If the patient has not received intensive induction chemotherapy in the past as a result of being unfit for chemotherapy, then the patient must have undergone at least one line of epigenetic modifier or other available therapy. If the patient has received intensive induction therapy, then the patient must have undergone at least two lines of therapy. If a patient has a FLT3 or IDH mutation, prior therapy must include a FLT3 or an IDH inhibitor. Relapse is defined as the recurrence of excess leukemic blasts in the marrow after previously achieving a complete remission, or complete remission with incomplete count recovery. Refractory refers to persistent excess leukemic blasts after two cycles of standard anthracycline containing induction, or one cycle of a high dose cytarabine containing regimen, or one cycle of a non-intensive regimen.
Calculated Creatinine clearance (CrCl) > 60 mL/min (based upon the Cockcroft- Gault Equation [CrCl = (140-age) * ideal body wt (in kg) * (0.85 if female) / (72 * Cr)]. Estimate Ideal body weight in (kg) Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet. Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.
Has recovered from the toxic effects of prior therapy to their clinical baseline.
Disqualifiers
Pregnant or breast feeding females are excluded.
Previous hematopoietic cell transplant.
Patients who are currently receiving another investigational agent are excluded.
Patients who have had chemotherapy (e.g., HMA therapy, chemotherapy, immunotherapy) or participation in any investigational drug treatment within 2 weeks or 5-half lives, whichever is more, of initiation of rebecsinib or at any time during the study.
Trial design
Design model
Sequential
Treatments tested in this trial
rebecsinib
DrugRebecsinib is administered by intravenous infusion on Days 1, 4, 8, and 11 of the 28 day cycle. Doses to be tested are 0.2, 0.4, 0.6, 0.8, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, and 8.0 mg/kg based in ideal body weight (IBW).
Treatment groups
No treatment groups listed
Trial outcomes
Primary outcomes
1
Determine the Maximum Tolerated Dose
Find the rate of dose limiting toxicities (DLTs) to establish the maximum tolerated dose (MTD) or biologically active dose of rebecsinib when given on days 1, 4, 8, and 11 of each 28 days cycle.
Time frame
From first dose through 28 days after initial dose for dose all finding cohorts, approximately 2 years.2
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
To determine the safety and tolerability of rebecsinib by ongoing evaluation of treatment-emergent adverse events (AEs) by collecting description, timing, grade \[CTCAE v5.0\], severity, seriousness, and relatedness of all events.
Time frame
From enrollment to initiation of new therapy for each subject, approximately 4 months.Secondary outcomes
1
Assess Clinical Activity through Overall Response Rate using 2017 ELN Response Criteria
To assess clinical activity by evaluating overall response rate. Overall Response Rate (ORR): Percentage of patients achieving Complete Remission (CR) + Partial Remission (PR) as defined by the revised 2017 ELN response criteria for AML
Time frame
From enrollment through disease assessment that shows progression, approximately 4 months.2
Assess Clinical Activity through Duration of Response
To assess clinical activity by evaluating duration of response. Duration of response is defined as number of days from day of complete or partial remission to day of relapse
Time frame
From enrollment through disease assessment that shows progression, approximately 4 months3
Assess Clinical Activity through Progression Free Survival Using 2017 ELN Response Criteria
To assess clinical activity by evaluating progression free survival, defined by the revised 2017 ELN response criteria for AML
Time frame
From enrollment through disease assessment that shows progression, approximately 4 months4
Assess Clinical Activity through Overall Survival using the revised 2017 ELN response criteria for AML
To assess clinical activity by evaluating overall survival, defined by the revised 2017 ELN response criteria for AML
Time frame
From enrollment through disease assessment that shows progression, approximately 4 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Aspera Biomedicines, Inc.
Lead sponsor
Tempus AI
Collaborator
Source ClinicalTrials.gov