Clinical Trials /

Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)

NCT04666649

Description:

Evaluate the safety and tolerability of pegcrisantaspase in combination with venetoclax (Ven-PegC) and estimate the maximum tolerated doses and/or biologically active doses of Ven-PegC in patients with relapsed or refractory acute myeloid leukemia (R/R AML)

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)
  • Official Title: Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 2087GCCC
  • NCT ID: NCT04666649

Conditions

  • Relapsed or Refractory Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Venetoclax and pegcrisantaspaseCohort 400mg of Venetoclax, 1000 IU/m² of Pegcrisantaspase

Purpose

Evaluate the safety and tolerability of pegcrisantaspase in combination with venetoclax (Ven-PegC) and estimate the maximum tolerated doses and/or biologically active doses of Ven-PegC in patients with relapsed or refractory acute myeloid leukemia (R/R AML)

Detailed Description

      This research study is a non-randomized, open-label Phase Ib clinical trial evaluating
      venetoclax (Ven) administered orally daily in combination with pegcrisantaspase (PegC)
      administered IV biweekly, as part of a 28-day treatment cycle in adult subjects with relapsed
      or refractory acute myeloid leukemia (R/R AML).

      The trial will consist of dose escalation to evaluate the safety and tolerability of Ven-PegC
      and estimate the maximum tolerated doses (MTDs) and/or biologically active doses (e.g.
      recommended phase 2 doses [RP2Ds]) of Ven-PegC in patients with R/R AML

      Venetoclax is an FDA (the U.S. Food and Drug Administration) approved drug, but this
      combination ( Ven-PegC) has not been approved by the FDA.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 400mg of Venetoclax, 500 IU/m ² of PegcrisantaspaseExperimentalThe subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 500 IU/m ² of Pegcrisantaspase in an IV every 14 days ( per cycle)
  • Venetoclax and pegcrisantaspase
Cohort 400mg of Venetoclax, 750 IU/m ² of PegcrisantaspaseExperimentalThe subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 750 IU/m ² of Pegcrisantaspase in an IV every 14 days ( per cycle)
  • Venetoclax and pegcrisantaspase
Cohort 400mg of Venetoclax, 1000 IU/m² of PegcrisantaspaseExperimentalThe subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 1000 IU/m² of Pegcrisantaspase in an IV every 14 days ( per cycle)
  • Venetoclax and pegcrisantaspase
Cohort 600mg Venetoclax, 1000 IU/m ² of PegcrisantaspaseExperimentalThe subject will take 600mg of Venetoclax every day as a pill by mouth and a dose of 1000 IU/m ² of Pegcrisantaspase in an IV every 14 days ( Per cycle)
  • Venetoclax and pegcrisantaspase

Eligibility Criteria

        Inclusion Criteria:

          -  A histologically or pathologically confirmed diagnosis of AML based on 2016 WHO
             classification. Patients with Complex Karyotype AML (CK-AML) and TP53-mutated AML are
             eligible for this study.

          -  AML has relapsed after or is refractory to, first-line therapy, with a maximum of
             three prior lines of therapy. Patients whose AML has FLT3 or IDH1/IDH2 mutations
             should have received at least one available FLT3 or IDH1/IDH2 inhibitors

          -  Age 18 years and older

          -  ECOG performance status ≤ 2

          -  Patients who have undergone allo-HSCT are eligible if they are ≥ 30 days post stem
             cell infusion, have no evidence of graft versus hose disease ( GVHD ) > Grade 1, and
             are ≥ 10 days off all immunosuppressive therapy

          -  Previous cytotoxic chemotherapy must have been completed at least 10 days prior to day
             1 of treatment on the study and all AEs (excluding alopecia, acne, rash) due to agents
             administered earlier should have recovered to < Grade 1. Patients with hematologic
             malignancies are expected to have hematologic abnormalities at study entry. These
             abnormalities which are thought to be primarily related to the underlying leukemia,
             are not considered to be toxicities (AE) and do not need to resolve to < Grade 1

          -  All biologic agents including hematopoietic growth factors must have been stopped at
             least 1 week prior to day 1 of treatment on the study

          -  Patients must have adequate organ function as defined below:

               -  Direct bilirubin ≤2X the institutional upper limit of normal (ULN) (except in
                  patients with leukemic infiltration of the liver)

               -  AST(SGOT)/ALT(SGPT) ≤3X ULN (except if attributable to leukemic infiltration of
                  the liver)

               -  Alkaline phosphatase ≤5X ULN

               -  Creatinine Clearance (CrCl) ≥ 45 mL/min (except in patients with evidence of
                  tumor lysis syndrome)

               -  Patients with a history of CNS leukemia must be stable with clear CSF for > 2
                  months prior to day 1 of treatment (patient can receive intrathecal maintenance
                  chemotherapy)

          -  Female patients of childbearing potential must have a negative pregnancy test <1 week
             prior to enrollment. Female patients of childbearing potential who are sexually active
             and male patients who are sexually active and have female partners of childbearing
             potential must agree to use highly effective method of contraception with their
             partners during exposure to study drugs and for 30 days after the last dose of study
             drugs.

          -  Ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients receiving any other investigational agents, or concurrent chemotherapy or
             immunotherapy

          -  Patients with acute promyelocytic leukemia (APL) confirmed with t(15;17) (i.e. FAB
             subtype M3 and M3 variant)

          -  Prior treatment with any asparaginase product. Patients who received ≤12 weeks of a
             BCL-2 inhibitor including venetoclax are eligible.

          -  Absolute peripheral blast > 100,000/μL. Hydroxyurea for blast count control is
             permitted before starting treatment and up to maximum of 10 days after starting
             treatment on the study. The decision to start hydroxyurea during this time is at the
             discretion of the treating physician.

          -  Patients with the following clinical histories are excluded:

               -  severe pancreatitis not related to cholelithiasis. Severe acute pancreatitis is
                  defined by lipase elevation >5X ULN and with signs or symptoms

               -  unprovoked deep venous thrombosis (DVT)

               -  pulmonary emboli

               -  hemorrhagic or thromboembolic stroke

               -  other malignancies requiring systemic chemotherapy, immunotherapy or targeted
                  therapy in the last three months

          -  Active, uncontrolled infection; patients with infection under active treatment and
             controlled with antibiotics are eligible

          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic
             congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
             illness/social situations that per site Principal Investigator's judgment would limit
             compliance with study requirements

          -  Pregnant women and female patients who are lactating and do not agree to stop breast-
             feeding.

          -  Uncontrolled active seizure

          -  Any other clinical conditions that in the opinion of the investigator would make the
             subject unsuitable for the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of regimen limiting toxicities (RLTs)
Time Frame:One year (after 12 cycle's treatment)
Safety Issue:
Description:The period for determination of RLT will be from the first day of treatment until 30 days after receiving the first dose of Ven-PegC.

Secondary Outcome Measures

Measure:The rate of CR
Time Frame:One year (after 12 cycle's treatment)
Safety Issue:
Description:Complete Remission rate
Measure:The rate of composite complete remission (CR+CRh+CRi+CRp)
Time Frame:One year (after 12 cycle's treatment)
Safety Issue:
Description:The rate of Complete Remission rate, Complete Remission with Partial hematological recovery, Complete Remission with incomplete hematological recovery and Complete Remission with incomplete platelet recovery.
Measure:Event-free Survival (EFS)
Time Frame:One year (after 12 cycle's treatment)
Safety Issue:
Description:Event-free Survival (EFS)
Measure:Overall Survival (OS)
Time Frame:One year (after 12 cycle's treatment)
Safety Issue:
Description:Overall Survival (OS)
Measure:The rate of conversion from transfusion dependence to transfusion independence
Time Frame:One year (after 12 cycle's treatment)
Safety Issue:
Description:The rate of conversion from transfusion dependence to transfusion independence
Measure:The rate of proceeding to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after administration of Ven-PegC
Time Frame:One year (after 12 cycle's treatment)
Safety Issue:
Description:The rate of proceeding to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after administration of Ven-PegC
Measure:Achievement of MRD <0.02% within 2 cycles of treatment with Ven-PegC
Time Frame:Two months
Safety Issue:
Description:Achievement of Minimal Residual Disease <0.02% within 2 cycles of treatment with Ven-PegC
Measure:Overall incidence and severity of AEs
Time Frame:One year (after 12 cycle's treatment)
Safety Issue:
Description:Overall incidence and severity of Adverse Events

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Maryland, Baltimore

Trial Keywords

  • Pegcrisantaspase
  • Venetoclax
  • Relapsed or refractory acute myeloid leukemia (R/R AML)
  • Ven-PegC
  • Maximum tolerated doses
  • Recommended phase 2 doses
  • Incidence of regimen limiting toxicities
  • Incidence of treatment-emergent adverse events

Last Updated

May 14, 2021