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

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ClinicalTrials.gov Identifier: NCT04666649

Recruitment Status : Recruiting

First Posted : December 14, 2020

Last Update Posted : May 19, 2022

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Ashkan Emadi, MD, PhD, University of Maryland, Baltimore

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Relapsed or Refractory Acute Myeloid Leukemia	Drug: Venetoclax and pegcrisantaspase	Phase 1

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	30 participants
Allocation:	Non-Randomized
Intervention Model:	Sequential Assignment
Intervention Model Description:	Cohort1: The subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 500 IU/m² of Pegcrisantaspase in an IV every 14 days ( per cycle) Cohort 2: The subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 750 IU/m² of Pegcrisantaspase in an IV every 14 days ( per cycle) Cohort 3: The subject will take 400mg 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) Cohort 4: The 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)
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia
Actual Study Start Date :	March 10, 2021
Estimated Primary Completion Date :	September 1, 2024
Estimated Study Completion Date :	September 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Familial acute myeloid leukemia with mutated CEBPA Cytogenetically normal acute myeloid leukemia Core binding factor acute myeloid leukemia

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

Drug Information available for: Venetoclax

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Acute Graft Versus Host Disease

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 400mg of Venetoclax, 500 IU/m ² of Pegcrisantaspase The 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)	Drug: Venetoclax and pegcrisantaspase Therapeutic
Experimental: Cohort 400mg of Venetoclax, 750 IU/m ² of Pegcrisantaspase The 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)	Drug: Venetoclax and pegcrisantaspase Therapeutic
Experimental: Cohort 400mg of Venetoclax, 1000 IU/m² of Pegcrisantaspase The 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)	Drug: Venetoclax and pegcrisantaspase Therapeutic
Experimental: Cohort 600mg Venetoclax, 1000 IU/m ² of Pegcrisantaspase The 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)	Drug: Venetoclax and pegcrisantaspase Therapeutic

Outcome Measures

Primary Outcome Measures :

Incidence of regimen limiting toxicities (RLTs) [ Time Frame: One year (after 12 cycle's treatment) ]
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.
Incidence of treatment-emergent adverse events (TEAE) [ Time Frame: One year (after 12 cycle's treatment) ]
The period for determination of TEAE will be from the first day of treatment until 30 days after receiving the first dose of Ven-PegC.

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04666649

Contacts

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Contact: Ashkan Emadi, M.D.,Ph.D.	410-328-6841	aemadi@umm.edu
Contact: Sunita Sunita	410-328-8199	sphilip1@umm.edu

Locations

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United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center	Recruiting
Baltimore, Maryland, United States, 21201
Contact: Clinical Trials Office - Greenebaum Cancer Center at Universit 800-888-8823

Sponsors and Collaborators

University of Maryland, Baltimore

Investigators

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Principal Investigator:	Ashkan Emadi, M.D.,Ph.D.	University of Maryland, Baltimore

More Information

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Responsible Party:	Ashkan Emadi, MD, PhD, Professor of Medicine and Pharmacology University of Maryland, School of Medicine Associate Director for Clinical Research, University of Maryland, Baltimore
ClinicalTrials.gov Identifier:	NCT04666649
Other Study ID Numbers:	2087GCCC
First Posted:	December 14, 2020 Key Record Dates
Last Update Posted:	May 19, 2022
Last Verified:	May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Ashkan Emadi, MD, PhD, University of Maryland, Baltimore:


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

Additional relevant MeSH terms:

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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type	Neoplasms Venetoclax Antineoplastic Agents

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