A Study of Rebecsinib for Patients With Relapsed/Refractory Secondary Acute Myeloid Leukemia or High Risk Myelofibrosis

A Phase 1 Study of Rebecsinib, a Spliceosome Modulator That Inhibits ADAR1, in Patients With Relapsed or Refractory Secondary Acute Myeloid Leukemia or Higher-Risk Myelofibrosis

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Myelofibrosis; Secondary AML
• Intervention / Treatment: Drug: rebecsinib

Detailed Description

The primary objective is to determine the maximum tolerated dose or biologically active dose of rebecsinib when given on days 1, 4, 8, and 11 of each 28 days cycle to patients with relapsed or refractory secondary acute myeloid leukemia (sAML), who have evolved from Myelodysplastic Syndrome (MDS) or myeloproliferative neoplasms (MPNs), or patients with higher-risk myelofibrosis. The other primary objective is to determine the safety and tolerability of rebecsinib by ongoing evaluation of adverse events (AEs), as assessed according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0).

Study outcomes will be measured by adverse event data, response rates, progression free survival and overall survival. Pharmacodynamics and plasma pharmacokinetics of rebecsinib will be explored.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Karla Mack; Phone Number: 443-253-0645; Email: kmack@asperabio.com
• Study Contact Backup: Name: Curis L Scribner, MD; Phone Number: 510-914-8368; Email: cscribner@asperabio.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92093
      • UC San Diego Moores Cancer Center
      • Contact: James Mangan, MD, PhD; Phone Number: 858-822-6381; Email: jmangan@health.ucsd.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to understand and the willingness to sign a written informed consent.
2. 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.
3. 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.
4. Has recovered from the toxic effects of prior therapy to their clinical baseline.
5. Subjects must be aged 18 years or older.
6. Both men and women of all races and ethnic groups are eligible for this trial.
7. Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study. Both men and women must agree to use a barrier method of contraception for the duration of the study and until 10 weeks after the final dose of rebecsinib.
8. Women of child-bearing potentialmust have a negative serum or urine pregnancy test.
9. For sAML and high risk MF, at relapse must have ≥5% leukemic bone marrow blasts.
10. Subjects must have an ECOG performance status of 0-2.
11. Hemoglobin ≥ 8.0 g/dL. This is to alleviate immediate concomitant need for transfusion via institutional guidelines for transfusion for symptomatic anemia.
12. Total bilirubin ≤ 1.5 times upper limit of normal.
13. ALT and AST ≤ 1.5 times upper limit of normal
14. Prothrombin time international normalized ratio (INR) ≤ 2; AND Partial thromboplastin time ≤ 1.66 times upper limit of normal.

Exclusion Criteria:

1. Pregnant or breast feeding females are excluded.
2. Previous hematopoietic cell transplant.
3. Patients who are currently receiving another investigational agent are excluded.
4. 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.
5. Current infection requiring systemic antibiotics.
6. Active infection with HIV, HBV, or HCV.
7. Concurrent malignancy or prior malignancy within the previous 3 years (other than completely resected carcinoma in situ or localized non-melanoma skin cancer).
8. Known central nervous system (CNS) involvement by malignancy.
9. Untreated autoimmunity such as autoimmune hemolytic anemia or immune thrombocytopenia.
10. Known uncompensated hypothyroidism (defined as TSH greater than 2x upper limit of normal not treated with replacement hormone).
11. Insufficient recovery from surgery-related wound healing.

12. Impaired cardiac function including any of the following:

    1. Myocardial infarction within 6 months of starting study drug;
    2. A past medical history of clinically significant ECG abnormalities, including QTc 470 msec or greater.
    3. Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
13. A QT ->470 msec on ECG.
14. On medication that is an inducer or inhibitor of CYP3A4, CYP2C9, CYP2C19, CYP2B6 and hepatic uptake transporters (e.g. OATP1B1/3, OAT1/2 OCT 1/2), or is metabolized by CYP2C9, 2C19, and 2B6. If they are an inducer or inhibitor or a known substrate of CYP2B6, CYP2C9, and CYP2C19 where minimal changes in drug concentration may lead to serious adverse reactions, the drug should be withdrawn for a minimum of 5 half lives or particular attention should be paid to toxicities or appropriate dose modifications to these drugs made.
15. Patients who in the opinion of the investigator may be unable to comply with the safety monitoring requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose through 28 days after initial dose for dose all finding cohorts, approximately 2 years.
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.	From enrollment to initiation of new therapy for each subject, approximately 4 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From enrollment through disease assessment that shows progression, approximately 4 months.
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	From enrollment through disease assessment that shows progression, approximately 4 months
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	From enrollment through disease assessment that shows progression, approximately 4 months
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	From enrollment through disease assessment that shows progression, approximately 4 months

Collaborators and Investigators

• Sponsor: Aspera Biomedicines, Inc.
• Collaborators: Tempus AI
• Investigators: Principal Investigator: James Mangan, MD, PhD, UC San Diego Moores Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: August 1, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: MF; sAML
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Hemic and Lymphatic Diseases; Primary Myelofibrosis
• Other Study ID Numbers: ASPE-01-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No