Clinical Trials Logo

Clinical Trial Summary

The primary objective of the Phase 1 part of the study is to determine the recommended dose of APVO436 administered intravenously to patients with AML or MDS. The primary objective of the Phase 1b part of the study is to evaluate the clinical activity of APVO436 in patients with AML or MDS. APVO436 is being studied in this Phase 1b, open-label, multi-center, two-part dose-escalation/dose expansion study to evaluate the safety, pharmacokinetic/pharmacodynamic (PK/PD), and clinical activity of APVO436 in patients with AML and MDS. The study will be conducted in 2 parts. The first part of this Phase 1B study is an open-label, multiple dose ascending dose escalation phase to determine the recommended dose (RP2D) level of APVO436 for future Phase 2 studies. The goal of the dose expansion phase of the study (Part 2) is to (i) evaluate the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care and (ii) obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities. Study Objectives for Dose Escalation Phase - Primary Objectives are to: 1. Determine the RP2D level of APVO436 administered intravenously (IV) in patients with AML or MDS, and 2. 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 APVO436-containing experimental monotherapy and combination therapy modalities. - Secondary Objectives are to: 1. Define the safety profile and immunogenicity of APVO436; to determine the PK/PD of APVO436; to evaluate the clinical activity of APVO436 in AML and MDS patients. 2. Further evaluate the safety profile and immunogenicity of APVO436 and the PK/PD of APVO436 and the relationship between PK/PD and clinical response. Study Objectives for Dose Expansion Phase - Primary Objective 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. - Secondary Objective is to obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities.


Clinical Trial Description

Part 1 - Dose Escalation: Dosing will start at the minimum anticipated biologic effect level (MABEL) in single-patient cohorts for the first 3 dose cohorts up to and including 3 mcg. Patients enrolled will have either: 1) relapsed or refractory AML and refuse or are not eligible for intensive chemotherapy or an allogeneic stem cell transplant, or 2) relapsed or refractory MDS and have > 5% blasts in the marrow or any circulating blasts in the peripheral blood and have failed a prior hypomethylating agent (HMA); failure is defined as intolerance to HMA, lack of response (no CR by at least 6 cycles), or have IWG defined progressive disease during or after treatment with an HMA. In single-patient Cohorts 1 to 3, the next dose cohort will only enroll after the patient in the current dose cohort has completed the first cycle of dosing (4 weeks) and no Grade ≥ 2 adverse events (AEs) (hematologic or non-hematologic) have occurred. If any Grade ≥ 2 AE occurs in the single-patient cohorts, then that cohort and all subsequent single-patient cohorts will be expanded to a 3 + 3. The next dose cohort in the 3 + 3 cohorts (all cohorts beyond Cohort 4) is started after patients in the previous dose cohort have completed the first cycle of dosing and an evaluation of AEs for DLTs during the DLT observation period has been completed. For the first 2 patients within each dose cohort, administration of the first dose must be separated by a minimum of 36 hours. At the conclusion of each cycle, patients with significant cytopenias without evidence of leukemia will have the dose delayed. Beginning in Cohort 5, and for all cohorts going forward, stepped dosing will be introduced to mitigate against the development of infusion-related reactions and cytokine release syndrome. Patients will receive APVO436 intravenously for six 28 day cycles, unless disease progression, intolerable toxicity, or withdrawal of consent occurs earlier. There is an option for longer treatment if the patient is responding. The RP2D level will be based on clinical activity, safety, incidence of DLTs, PK, and PD in each dose cohort. Part 2 - Dose Expansion: The MTD for APVO436 was not reached at a dose level of 240 µg/cycle (Cohort 10 in the dose escalation phase). The sub-MTD dose level of Cohort 6A was identified as the RP2D level of APVO436 for further evaluation during the expansion phase. In the open-label, multi-center, dose expansion phase of the study (Part 2), a total of 90 primary AML patients will be enrolled into 5 cohorts of 18 patients each. The goal of this expansion phase of the 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 APVO436-containing experimental monotherapy and combination therapy modalities. In Cohorts 1-4, APVO436 will be administered at a fixed dosage of 18 mcg after a weekly ramp up during Cycle 1 (Cohorts 1, 3, 4) or Cycle 1-2 (Cohort 2). In Cohort 5, APVO436 will be administered at a fixed dose of 18 mcg twice weekly after a weekly ramp up during Cycle 1. The specific patient populations and experimental treatments for the expansion phase are as follows: Cohort 1. Induction with Chemotherapy (ChT) plus APVO436. 1st or 2nd Early Relapse. Patients may receive either Ara-C intermediate dose (IDAC) or MEC as the ChT backbone. Fit primary or secondary AML patients (Age: >18 years) in 1st or 2nd relapse with last CR <12 months or primary refractory disease will receive 4 x 28-day cycles of combined 2-drug immunochemotherapy: APA [APVO436+Intermediate dose ARA-C (IDAC) or APMEC [APVO436+MEC]. Cohort 2. Induction with APVO436 + Venetoclax + Azacitidine - Frontline or 1st Relapse. Poor prognostic but fit primary or secondary AML patients (Age >18 years) who are treatment-naïve or in 1st relapse will receive 4 x 28-day cycles of combined 3-drug immunochemotherapy: APVA [APVO436+Venetoclax+Azacitidine]. Cohort 3: Consolidation post 7+3 - Frontline + 1st Relapse. Fit primary AML patients (Age: >18 years) with FLT3-negative intermediate or adverse risk AML (including but not limited to: TP53, RUNX1 and ASXL1 mutations and/or complex cytogenetics) who are treatment-naïve or in 1st relapse with a duration of CR1<1 year will receive 4 x 28-day cycles of immunotherapy with APVO436 after hematologic recovery (ANC>1,000/µL; Hgb ≥9 g/dL; Plt≥100,000/µL) post induction. Cohort 4: MRD-positive (MRD+) 1st Remission, APVO436 + Azacitidine combination. >18 years old MRD+ (at ≥0.1% level by multicolor-multiparameter flow cytometry [MFC] in Central Lab) high-risk 1st remission AML patients will be treated with 4 x 28-day cycles of APVO436 + oral azacitidine (Onureg, CC-486). Cohort 5: MRD+ 2nd Remission, Single Agent APVO436. >18 years old MRD+ (at ≥0.1% level by MFC in Central Lab) AML patients who are in 2nd remission post-induction with a standard of care regimen will be treated with 4 x 28-day cycles of APVO436 monotherapy. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03647800
Study type Interventional
Source Aptevo Therapeutics
Contact SoYoung Kwon
Phone (206) 859-6604
Email KwonS@apvo.com
Status Recruiting
Phase Phase 1
Start date December 13, 2018
Completion date June 15, 2023

See also
  Status Clinical Trial Phase
Completed NCT03118466 - Mitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for Relapsed or Refractory Acute Myeloid Leukemia Phase 2
Not yet recruiting NCT06313437 - Revumenib in Combination With 7+3 + Midostaurin in AML Phase 1
Withdrawn NCT03444649 - Epacadostat, Idarubicin and Cytarabine (EIC) in AML Phase 1
Withdrawn NCT02905994 - Volasertib Combined With Induction Chemotherapy in Acute Myeloid Leukemia Phase 1
Recruiting NCT02261779 - Phase I/II Trial of ATRA and TCP in Patients With Relapsed or Refractory AML and no Intensive Treatment is Possible Phase 1/Phase 2
Completed NCT00333190 - CD8+ T Cell Depletion for GVHD Prophylaxis After Peripheral Blood Stem Cell Transplantation N/A
Completed NCT00246649 - Stem Cell Transplant With Specially Treated Cells in Treating Patients With Acute Leukemia N/A
Terminated NCT04079738 - Study Augmenting TAK-659 Action in Relapsed/Refractory AML by Addition Ofthe Proteasome Inhibitor Ixazomib Phase 1/Phase 2
Completed NCT03466320 - DEPLETHINK - LymphoDEPLEtion and THerapeutic Immunotherapy With NKR-2 Phase 1/Phase 2
Withdrawn NCT03138395 - iCare3: Monitoring Circulating Cancer DNA After Chemotherapy in MDS and AML N/A
Terminated NCT01570465 - Prospective Study on Severe Infections on Acute Myeloid Leukemia (AML) Patients
Completed NCT04443751 - A Safety and Efficacy Study of SHR-1702 Monotherapy in Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) Phase 1
Terminated NCT03761069 - Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias Phase 1
Completed NCT02631993 - Photochemotherapy and Graft-versus-leukemia in Acute-leukemia N/A
Completed NCT02575963 - Lintuzumab-Ac225 in Older Acute Myeloid Leukemia (AML) Patients Phase 1/Phase 2
Completed NCT00780598 - Safety and Anti-Disease Activity of Oral Tosedostat (CHR-2797) in Elderly Subjects With Refractory or Relapsed AML Phase 2
Completed NCT00863148 - Allogeneic Stem Cell Transplant With Clofarabine, Busulfan and Antithymocyte Globulin (ATG) for Adult Patients With High-risk Acute Myeloid Leukemia/Myelodysplastic Syndromes (AML/MDS) or Acute Lymphoblastic Leukemia (ALL) Phase 2
Completed NCT00542971 - Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006) Phase 1/Phase 2
Completed NCT00761449 - Lenalidomide in High-risk MDS and AML With Del(5q) or Monosomy 5 Phase 2
Terminated NCT00176930 - Stem Cell Transplant for Hematological Malignancy N/A