- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05001828
Study of ADI-PEG 20, Venetoclax and Azacitidine in Acute Myeloid Leukemia
Phase IA/B Combination Study of ADI-PEG 20, Venetoclax and Azacitidine in Patients With Acute Myeloid Leukemia (AML)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is an open label, single arm, phase 1 trial with recommended phase 2 dose (RP2D) cohorts based on subject inclusion criteria.
Lead In: 6 patients will be enrolled to be treated with standard dose of azacitidine and venetoclax and the expected RP2D of ADI-PEG 20 (dose level 0). In case of DLT occurring in >1 patient in cycle 1, 6 additional patients will be accrued at dose level -1 of ADI-PEG 20 while keeping the doses of azacitidine and venetoclax unchanged (Dose level -1). Enrollment to cohort 1 and 2 will start after ≤1 patient out of 6 encounters DLT in cycle 1 at one of these dose levels. The 6 patients enrolled at that dose level will be counted for efficacy analysis in Cohort 1. Cohort 1: Relapsed or refractory AML: target response 25%. Historical expectation for venetoclax and azacitidine is 15%.
Cohort 2: Newly diagnosed high risk AML: Target response 55%. Historical expectation for venetoclax and azacitidine is 40%.
Treatment may be continued for a total of 24 cycles, each of 28 days.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Mirla Langlois
- Phone Number: 161 858-452-6688
- Email: mlanglois@polarispharma.com
Study Contact Backup
- Name: Nicole DeFord
- Phone Number: 619-808-5065
- Email: ndeford@polarispharma.com
Study Locations
-
-
Illinois
-
Skokie, Illinois, United States, 60077
- Recruiting
- Orchard Healthcare Research Inc
-
Contact:
- Joy Jardinico, RN
- Phone Number: 224-534-7580
- Email: jjardinico@orchardhr.com
-
Contact:
- Ofelia Hernandez
- Phone Number: 224-534-7580
- Email: ohernandez@orchardhr.com
-
-
North Carolina
-
Charlotte, North Carolina, United States, 28204
- Not yet recruiting
- Levine Cancer Institute
-
Contact:
- Kelly Bumgarner, RN
- Phone Number: 980-521-8696
- Email: Kelly.Bumgarner@atriumhealth.org
-
Contact:
- Neha Upadhyay, RN
- Phone Number: 980-442-2393
- Email: Neha.Upadhyay@atriumhealth.org
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- Md Anderson Cancer Center
-
Contact:
- Gautam Borthakur
- Phone Number: 713-563-1586
- Email: gborthak@mdanderson.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Cohort 1: Previously treated (relapsed/recurrent) or refractory AML based on the 2016 revision to the World Health Organization (WHO) criteria (Arber 2016)
- Cohort 2: Untreated AML per 2016 WHO (Arber 2016) criteria with high-risk features and not a candidate for intensive chemotherapy because of age 60 years or older, age-related comorbidities, cardiac disease, prior anthracycline use, high probability of treatment-related mortality, or otherwise would not benefit from intensive chemotherapy treatment.
- Age ≥ 18 years
- Life expectancy reasonably adequate for evaluating the treatment
- White blood cell (WBC) count of 10 × 109/L or less. (Use of hydroxyurea to control WBC is allowed till 48 hours prior to protocol treatment)
- Adequate renal function: Creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance > 40 mL/minute (measured or calculated according to the Cockcroft-Gault formula)
Adequate liver function
- Total bilirubin ≤ 1.5 x ULN
- ALT and AST both ≤ 2.5 x institutional ULN or ≤ 5 times the ULN for patients with leukemic involvement of liver
Exclusion Criteria:
Prior treatments as follows:
- Cohort 1: >2 cycles of prior combination treatment with venetoclax+hypomethelating agent (i.e. azacitidine, decitabine) is exclusionary. All other prior treatment for antecedent hematological disorders and/or for AML is permitted.
- Cohort 2: Prior treatment for antecedent hematological disorders with venetoclax or chemotherapy or any prior treatment for their AML is exclusionary. However, treatment with other agents, including hydroxyurea or ≤2 cycles of hypomethylating agent (i.e. azacitidine, decitabine), for MDS or myeloproliferative neoplasm is permitted.
- Cohort 2: Favorable risk AML per European LeukemiaNet (ELN) 2022 criteria (Döhner 2022)
- Known active CNS involvement by leukemia
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Previously Treated AML
Previously treated AML based on the revised 2017 European LeukemiaNet (ELN) criteria with age at least 18 years, and having ≥10% blasts in bone marrow or peripheral blood
|
ADI-PEG 20 in combination with venetoclax and azacitidine
Other Names:
|
Experimental: Untreated AML With High Risk Features
Untreated AML per ELN criteria with high risk features, or age ≥ 65 years and ineligible for intensive chemotherapy because of older than 75 years, cardiac disease or prior anthracycline use or high probability of treatment-related mortality
|
ADI-PEG 20 in combination with venetoclax and azacitidine
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Determine the RP2D of ADI-PEG 20 in combination with venetoclax and azacitidine, per the number of subjects with treatment-related adverse events by current CTCAE
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Determine preliminary evidence of tumor activity, per the revised 2017 European LeukemiaNet criteria
Time Frame: 2 years
|
2 years
|
Determine the peripheral blood arginine levels of ADI-PEG 20 in combination with venetoclax and azacitidine
Time Frame: 2 years
|
2 years
|
Determine the peripheral blood citrulline levels of ADI-PEG 20 in combination with venetoclax and azacitidine
Time Frame: 2 years
|
2 years
|
Determine the anti-drug antibodies of ADI-PEG 20 in combination with venetoclax and azacitidine
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: John S Bomalaski, Polaris Group
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- POLARIS2020-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Myeloid Leukemia, Adult
-
National Cancer Institute (NCI)Active, not recruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Adult Acute Monoblastic Leukemia | Adult Acute Monocytic Leukemia | Adult Acute Myeloid Leukemia With Maturation | Adult Acute Myeloid Leukemia Without Maturation | Adult Acute Myelomonocytic Leukemia | Alkylating Agent-Related Acute Myeloid... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Monoblastic Leukemia | Adult Acute Monocytic Leukemia | Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 | Adult Acute Myeloid Leukemia With Maturation | Adult Acute Myeloid Leukemia With Minimal Differentiation | Adult Acute... and other conditionsUnited States
-
National Cancer Institute (NCI)TerminatedAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome | Recurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia in Remission | Adult Acute Monoblastic Leukemia | Adult Acute Monocytic Leukemia and other conditionsCanada
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid Leukemia With t(8... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult Acute... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedSecondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Adult Acute Monoblastic Leukemia | Adult Acute Monocytic Leukemia | Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 | Adult Acute Myeloid Leukemia With Maturation | Adult Acute Myeloid Leukemia With Minimal... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedAdult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult Acute Myeloblastic Leukemia Without Maturation... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedAdult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult Acute Myeloblastic Leukemia Without Maturation... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid Leukemia With t(8... and other conditionsUnited States
-
Nohla Therapeutics, Inc.National Cancer Institute (NCI); Fred Hutchinson Cancer CenterCompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult Acute... and other conditionsUnited States
Clinical Trials on ADI-PEG 20
-
FDA Office of Orphan Products DevelopmentCompleted
-
Ludwig Institute for Cancer ResearchMemorial Sloan Kettering Cancer Center; NYU Langone HealthCompletedSkin Cancer | Metastatic Melanoma | NeoplasmUnited States
-
Barts & The London NHS TrustCancer Research UK; UK: Barts Center for Experimental Cancer Medicine (CECM)...UnknownMalignant Pleural MesotheliomaUnited Kingdom
-
University of MiamiCompletedMelanoma (Skin)United States
-
Ludwig Institute for Cancer ResearchMemorial Sloan Kettering Cancer Center; National Taiwan University Hospital; Duke... and other collaboratorsTerminatedSmall Cell Lung CancerUnited States, Taiwan, Germany, Belgium, United Kingdom
-
Polaris GroupCompletedHER2 Negative Metastatic Breast CancerUnited States
-
Polaris GroupTerminatedGlioma | Hepatocellular Carcinoma | Uveal Melanoma | Sarcomatoid Carcinoma | Pleural Mesothelioma Malignant Advanced | Peritoneal Mesothelioma Malignant Advanced | Non-squamous Non-small Cell Lung CarcinomaUnited States, United Kingdom
-
Polaris GroupTerminatedHepatocellular Carcinoma | Gastric Cancer | Colorectal Cancer | Advanced Gastrointestinal (GI) MalignanciesUnited States, Taiwan, Korea, Republic of, United Kingdom, China, Italy
-
Polaris GroupCompletedArgininosuccinate Synthetase DeficientUnited States
-
Polaris GroupCompletedAdvanced Pancreatic CancerUnited States