Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 4:58 AM
Ignite Modification Date:
2025-12-25 @ 4:58 AM
NCT ID:
NCT04973618
Brief Summary:
The goal of this Phase IB study is to evaluate the safety and tolerability of APVO436 in naïve elderly unfit patients with newly diagnosed primary AML at the RP2D level when it is used as an adjunct to the standard of care and obtain a preliminary assessment of the anti-leukemia activity of an APVO436-containing combination therapy.
Study Objectives:
\- Primary Objective: Evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care (venetoclax and azacitidine).
\- Secondary Objectives:
* Obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental triple drug combination therapy modalities.
* Determine pharmacodynamics (PD) of APVO436, including changes in CD123 antigen density and measures of T cell number and function over time.
* Determine correlations between response and MRD level and cytogenetic and molecular genetic profiles.
Detailed Description:
The goal of this Phase IB study is to evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care and obtain a preliminary assessment of the anti-leukemia activity of an APVO436-containing combination therapy.
The MTD for APVO436 was not reached at a dose level of 240 µg/cycle in the ongoing Phase 1 FIHT (Cohort 10 in the dose escalation phase; weekly dose 60 mcg). 46 patients have received intravenous infusions of APVO436 across multiple dose-escalation cohorts, with dosing escalated from 0.3 micrograms to 60 micrograms. Long half-life of APVO436 enabled its administration over short infusion times. APVO436 exhibited a manageable safety profile, encouraging single agent activity and a promising benefit to risk profile in relapsed advanced stage AML. Of 7 evaluable relapsed AML patients treated in Cohort 6, 5 showed stabilization of their leukemia. Of the 5 AML patients with disease stabilization, 3 lived 246+ days, 261+ days, and 281+ days, respectively and 2 progressed after a month. Two of the patients who experienced a stabilization of their relapsed leukemia achieved first a partial remission (PR) and subsequently a complete remission (CR). No partial or complete remissions were observed at APVO436 dose levels lower or higher than the Cohort 6 dose level. The sub-MTD dose level of Cohort 6 was identified as the RP2D level of APVO436 for further evaluation in this study. Therefore, APVO436 will be used at the Cohort 6 dose level from Study 5001 in this study. CRS has occurred in some patients and has been managed using the generally recommended standard CRS treatments". In Cohort 6, among 9 AML/MDS patients evaluable for toxicity, 2 patients developed a Grade 1 CRS and one patient developed a transient Grade 3 CRS related to APVO436 which resolved with routine clinical management.
A total of 20 eligible patients will be enrolled in the current study. APVO436 will be administered intravenously over 4 hours weekly on days 1, 8, 15, and 22 of each cycle at a fixed dosage of 18 mcg after a weekly ramp up during Cycle 1 (Step-up dosing: C1D15: 6 mcg over 22 hours, C1D22: 12 mcg over 8 hours, C2D1: 18 mcg over 6 hours, C2D8: 18 mcg over 4 hours). The infusion time may be increased to 22 hours if deemed appropriate and/or necessary by the PI.
Patients will receive 4 x 28-day cycles of combined 3-drug immunochemotherapy: APVA \[APVO436+Venetoclax+Azacitidine\]
Optional continued triple therapy for 4 additional cycles (up to 8 total cycles) will be available for patients with an objective working group response or prolonged stable disease/clinical benefit. Patients completing 8 cycles of triple therapy on protocol will then move to follow-up and continue SOC therapy per their treating physician.
Venetoclax will be administered orally daily on days 1-21 of each cycle at a fixed dosage of 400 mg/daily after a daily ramp up (Day 1: 100 mg; Day 2: 200 mg; Day 3-Day 21: 400 mg). Standard dose adjustments will be made for patients on azole antifungals.
Azacitidine will be administered intravenously over 30 min daily on days 1-7 of each cycle at a dosage of 75 mg/m2
Study:
NCT04973618
Study Brief:
Protocol Section:
NCT04973618