TP-0903 for the Treatment of FLT3 Mutated Acute Myeloid Leukemia

NCT04518345 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-19229NCI-2020-04292
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase IB/II trial studies the best dose of TP-0903 and how well it works when given alone or with azacitidine in treating patients with FLT3 gene mutated acute myeloid leukemia. TP-0903 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving TP-0903 alone or with azacitidine may kill more cancer cells.

Conditions

Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose of dubermatinib (TP-0903)

  Determine a tolerable dose of TP-0903 monotherapy for relapsed/refractory patients with FLT3 AML.

  Up to 28 days

• Composite complete response (CR) rate

  Will calculate the composite CR rate (complete remission \[CR\]/complete remission with incomplete count recovery \[CRh) defined according to the 2017 European LeukemiaNet Acute Myeloid Leukemia recommendation.

  Up to 5 years post registration

• Composite CR rate with partial hematologic recovery (CRh) rate

  Will calculate the composite CR rate (CR/CRh), defined according to the International Working Group criteria and assessed at the end of induction.

  through study completion, an average of 1 year

Secondary Outcomes (6)

• Disease-free survival

  From the date of first CR/CRh until the first date of relapse/progression or death from any cause, assessed up to 5 years post registration

• The Number of patients who proceed to transplant

  Up to 5 years post registration

• Overall survival

  From the treatment start date until the date of death from any cause or date last known alive, assessed up to 5 years post registration

• Maximum grade of each type of adverse event

  Up to 5 years post registration

• Incidence of treatment-related adverse events

  Up to 5 years post registration

Other Outcomes (5)

• Peak Plasma Concentration (Cmax) pharmacokinetics (PK)

  Up to 5 years post registration

• Area under the plasma concentration (AUC) pharmacokinetics (PK)

  Up to 5 years post registration

• Changes in cytokines/chemokines

  Up to 5 years post registration

Study Arms (1)

Treatment (dubermatinib)

EXPERIMENTAL

FLT3 AML WITH RELAPSED/REFRACTORY DISEASE: INDUCTION: Patients receive dubermatinib PO QD on days 1-21. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients with clinical or hematologic response and not transplant eligible may continue dubermatinib until loss of response/clinical benefit. Patients with clinical or hematologic response and transplant eligible may continue dubermatinib until one week prior to admission.

Drug: Azacitidine; Drug: Dubermatinib

Interventions

Azacitidine DRUG

Given IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (dubermatinib)

Dubermatinib DRUG

Given PO

Also known as: TP 0903, TP-0903, TP0903

Treatment (dubermatinib)

Eligibility Criteria

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

You may qualify if:

• Patients with AML and the presence of FLT3-ITD mutation
• Patients with secondary AML or therapy related disease (t-AML) are eligible
• If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Total bilirubin \< 2.0mg/dL unless due to Gilbert's disease
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x institutional upper limit of normal
• Creatinine (Cr) clearance \> 50 mL/min by Cockcroft-Gault calculation
• New York Heart Association (NYHA) Congestive Heart Failure (CHF) class II or better
• Cardiac ejection fraction ≥40%
• Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
• Ability to understand and willingness to sign the written informed consent document
• Human immunodeficiency virus (HIV) infection without history of acquired immunodeficiency syndrome (AIDS) and sufficiently high CD4 cells (\> 400/mm\^3) and low HIV viral loads (\< 30,000 copies/ml plasma) not requiring anti-HIV therapy are eligible

You may not qualify if:

• Patients with acute promyelocytic leukemia
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Treatment with hydoxyurea is permitted during cycle 1 to maintain white blood cell (WBC) \< 40,000/uL
• Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
• Patients with active central nervous system (CNS) malignancy
• Major surgery within 2 weeks before day 1
• Uncontrolled active infection. Patients with infection requiring parenteral antibiotics are eligible if the infection is controlled
• Patients with significantly diseased or obstructed gastrointestinal tract
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV), unstable angina pectoris, myocardial infarction within 6 months prior to enrollment, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
• Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Pregnant women or women who are breastfeeding are excluded from this study. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women
• Patients with advanced malignant solid tumors
• Patients who are not able to swallow capsules or tablets

Sponsors & Collaborators

• Uma Borate: lead
• Sumitomo Pharma America, Inc.: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; dubermatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Uma Borate, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 30, 2020
• First Posted: August 19, 2020
• Study Start: November 5, 2020
• Primary Completion: October 13, 2021
• Study Completion: December 22, 2021
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)