New treatment for newly diagnosed Acute Myeloid Leukemia

A Phase 1b/2 Open-Label Study of APVO436 in Combination With Venetoclax and Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

This study is testing a new treatment combining APVO436 with two other drugs to see if it helps adults with newly diagnosed Acute Myeloid Leukemia feel better and stay safe from side effects.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Aptevo Therapeutics (Industry-sponsored)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 7 sites (Denver, Colorado and 6 other locations)
• Trial ID: NCT06634394 on ClinicalTrials.gov

What this trial studies

This is a multi-center, open-label, dose-finding study evaluating the safety and efficacy of APVO436 in combination with venetoclax and azacitidine in adult patients with newly diagnosed, CD123-positive Acute Myeloid Leukemia (AML). The study consists of 28-day treatment cycles across five sequential cohorts, with a focus on determining the optimal dosing of APVO436 while minimizing the risk of cytokine release syndrome (CRS). Participants will receive a series of priming doses followed by the determined cohort dose level of APVO436 administered via a 4-hour intravenous infusion.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed, CD123-positive AML who are not suitable for standard induction therapy.

Not a fit: Patients who have previously received treatment for AML or do not meet the specific eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with newly diagnosed AML who are ineligible for standard induction therapy.

How similar studies have performed: Other studies have shown promise with similar combination therapies in AML, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

* 1\. Age ≥18 years. 2. Patient must have confirmation of AML based on 2016 World Health Organization (WHO) criteria and not been previously treated.

  3\. Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry \[IHC\]). Confirmation at diagnosis is acceptable.

  4\. Patient must be considered ineligible for induction therapy defined by at least one of the following:
  1. ≥75 years of age
  2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3
  3. Cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
  4. Pulmonary disorder (e.g., DLCO ≤65% or FEV1 ≤65%)
  5. Creatinine clearance 30-45 mL/min based on Cockcroft-Gault or Modified of Diet in Renal Disease (MDRD) formular
  6. Hepatic disorder with total bilirubin between 1.5 and 3 times the ULN 5. Patient must have a projected life expectancy of ≥12 weeks

Exclusion Criteria:

1. Patient has received treatment with the following:

   1. A hypomethylating agent, venetoclax, and/or chemotherapeutic agent for AML, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or myelodysplastic/myeloproliferative neoplasms (MPS/MPN)
   2. CAR-T cell therapy or history of allogeneic hematopoietic stem cell transplant (HSCT)
   3. Experimental therapies for MDS or AML
2. Patient is currently participating in another interventional research study.
3. Patient has history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
4. Patient has acute promyelocytic leukemia.
5. Patient has a current autoimmune disorder requiring immunosuppressive therapy such as systemic (oral or IV) steroid therapy \>10 mg methylprednisolone daily or its equivalent
6. Patient is receiving concurrent corticosteroid therapy as an anticancer drug (any dose).
7. Patient has known active CNS involvement with AML. Patients who received intrathecal chemotherapy for prophylaxis of AML in the CNS prior to enrollment may enroll in this study.
8. Creatinine clearance \<30ml/min based on Cockcroft-Gault or MDRD formular.
9. Bilirubin of \>3xULN in the absence of Gilbert's Syndrome.
10. AST and/or ALT \>3 times the ULN.

Where this trial is running

Denver, Colorado and 6 other locations

• Colorado Blood Cancer Institute — Denver, Colorado, United States (Recruiting)
• University of Miami — Miami, Florida, United States (Recruiting)
• University of Kansas — Fairway, Kansas, United States (Recruiting)
• Gabrail Cancer Center — Canton, Ohio, United States (Recruiting)
• Oncology Hematology Care — Cincinnati, Ohio, United States (Recruiting)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Caroline Taromino

Conditions Acute Myeloid Leukemia