Clinical trial NCT06634394: APVO436 Phase 1b/2 Study in Patients With Newly Diagnosed AML
Official title: A Phase 1b/2 Open-Label Study of APVO436 in Combination With Venetoclax and Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Acute Myeloid Leukemia
Lead sponsor: Aptevo Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-10-09
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A multi-center, open-label, dose-finding study of five dose levels of APVO436 in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.

Detailed description: Phase 1b consists of 28-day cycles of treatment in five sequential cohorts. In Cycle 1 (C1) only, to reduce the risk of CRS, each cohort will receive 4 priming doses of APVO436 respectively. APVO436 will be given in combination with venetoclax and azacitidine. For C1D15 and all doses in each subsequent cycle, cohorts will receive APVO436 at the determined cohort dose level.

APVO436 dosing will be administered by a 4-hour intravenous (IV) infusion.

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.

Primary outcomes:
measure: To assess the safety, tolerability, and maximum tolerated dose (MTD) of increasing doses of APVO436 in combination with venetoclax/azacitidine in patients with newly diagnosed AML
timeFrame: Through the end study completion average of 1 year.
Secondary outcomes:
measure: Determine the efficacy of increasing doses of APVO436 in combination with venetoclax and azacitidine in patients with newly diagnosed AML
timeFrame: Through the end study completion average of 1 year.
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Fairway
country: United States
facility: University of Kansas
state: Kansas
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cincinnati,
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Aptevo Therapeutics
name: Dirk Huebner, MD
role: STUDY_DIRECTOR
References: