Study of Avatrombopag for Temozolomide-induced Thrombocytopenia in Glioma (APATIT-G)

NCT04931849 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: UCCS20154
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if using avatrombopag in patients with thrombocytopenia due to temozolomide treatment can safely improve a patient's platelet count and allow the patient to complete the temozolomide treatment course as planned.

Conditions

Thrombocytopenia

Keywords

Thrombocytopenia; Temozolomide; Avatrombopag; Temozolomide-induced Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• Safety of treatment

  Measure of time from study enrollment until progression.

  48 weeks

Study Arms (1)

Experimental: Avatrombopag

EXPERIMENTAL

Avatrombopag 40 mg daily by mouth (PO)

Drug: Avatrombopag

Interventions

Avatrombopag DRUG

Avatrombopag is a small molecule thrombopoeitic receptor agonist (TPO-RA) that mimics the biological effects of thrombopoeitin (TPO)

Experimental: Avatrombopag

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of grade 2, 3 or 4 glioma
• Subject has initiated concurrent RT and temozolomide followed by planned 6-12 cycles of temozolomide;
• Subject is willing and able to provide written informed consent;
• Subject is ≥ 18 years of age at the time of informed consent;
• Subject is willing and able to comply with all aspects of the protocol;
• Subject had platelet counts ≥ 100, 000/uL at the start of RT+TMZ or TMZ alone;
• Subject experienced grade ≥ 3 (moderate to severe) thrombocytopenia, defined by platelet counts ≤ 50 x 109/L, measured at least 24 hours apart, during the induction RT+TMZ, or at any time during the maintenance TMZ;
• Subject is able to continue to receive temozolomide regimen at the standard maintenance dose and schedule;
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
• Subject has a life expectancy \> 12 weeks at screening and is able to receive at least 2 additional cycles of TMZ;
• Females of childbearing potential must agree to use a highly effective method of contraception (combination of condom, diaphragm, or sponge with a spermicide) throughout the entire study period and for 28 days after the investigational product (IP) discontinuation;

You may not qualify if:

• History of hematologic malignancy, including leukemia, myeloma, myeloproliferative disease, lymphoma, or myelodysplastic syndrome;
• Subject with history of solid tumor and has received chemotherapy alone or chemotherapy and radiation in the past 5 years;
• Subject has received \> 2 previous lines of chemotherapy;
• Subjects who have previously received radiation treatments to the pelvic region including brachytherapy;
• Subject with an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 x upper limit of normal (ULN) or total bilirubin ≥ 3 x upper limit of normal;
• Subject is known to be human immunodeficiency virus positive;
• Known clinically significant acute or active bleeding (e.g., gastrointestinal or central nervous system) within 7 days of screening;
• Known history of thrombophilia with high risk of thrombosis (e.g., homozygous factor V Leiden mutation or prothrombin G20210A mutation, anti-thrombin deficiency, protein C deficiency, protein S deficiency, or antiphospholipid antibody syndrome);
• Subject has a medical condition that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study, such as unstable angina, renal failure requiring dialysis, or active infection requiring intravenous antibiotics;
• History of arterial or venous thrombosis within 6 months of screening;
• Subject has used vitamin K antagonist within 7 days of screening (use of low molecular weight heparin, factor Xa inhibitors, or direct thrombin inhibitors is allowed);
• Subject has a history of chronic platelet or bleeding disorder or thrombocytopenia due to another etiology other than temozolomide (e.g., chronic liver disease or immune thrombocytopenia purpura);
• Subject has used moderate or strong dual inducer of cytochrome P450 (CYP) 2C9 or CYP3A4/5 such as rifampin within 7 days of screening, and/or moderate or strong dual inhibitor such as fluconazole;
• Subject has previously received a thrombopoietin receptor agonist (e.g., eltrombopag or romiplostim) for the treatment of temozolomide induced thrombocytopenia;
• Subject has received a platelet transfusion within 3 days of screening;

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Thrombocytopenia

Interventions

avatrombopag

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor - Department of Medicine , Hematology/Oncology (SMD)

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 18, 2021
• Study Start: May 6, 2022
• Primary Completion: October 11, 2023
• Study Completion: July 18, 2024
• Last Updated: January 15, 2025

Record last verified: 2025-01

Locations

US (1)