Acute Myeloid LeukemiaEarly Phase 1NCT04518345
TP-0903 for the Treatment of FLT3 Mutated Acute Myeloid Leukemia
A Early Phase 1 study testing Azacitidine and Dubermatinib in people with Acute Myeloid Leukemia and Secondary Acute Myeloid Leukemia, run by Uma Borate at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Therapy-Related Acute Myeloid Leukemia
- What is being tested?
- Azacitidine and Dubermatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Nov 2020to 22 Dec 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: A Phase 1b/2 Study of TP-0903 in Patients With Acute Myeloid Leukemia and FLT3 Mutations
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine a tolerable dose of dubermatinib (TP-0903) monotherapy for relapsed/refractory patients with FLT3 acute myeloid leukemia (AML).
II. To determine the maximum tolerated dose (MTD) of TP-0903 with azacitidine in untreated unfit patients with FLT3 AML.
III. To determine the complete remission (CR) or complete remission with partial hematologic recovery (CRh) rate following induction therapy with TP-0903 in relapsed/refractory patients or TP-0903 with azacitidine therapy in untreated unfit patients with FLT3 AML.
SECONDARY OBJECTIVES:
- To determine the toxicity profile of TP-0903 as a single agent and in combination with or azacitidine.
II. To determine disease-free survival for patients achieving CR/CRh in each cohort.
III. To determine overall survival for patients in each cohort. IV. To determine the proportion of patients who go to transplant.
EXPLORATORY OBJECTIVES:
- To conduct pharmacokinetic studies of TP-0903 alone and in combination with azacitidine.
II. To examine changes in circulating AXL, Gas6, FLT3 ligand, and other cytokines/chemokines by TP-0903.
III. To determine the impact of TP-0903 on the inhibition of kinase signaling (AXL, FLT3, STAT5, AURKA), and metabolomics in AML cells.
IV. To determine differentially expressed genes in bone marrow stromal cells and AML cells upon TP-0903 treatment.
- To examine sensitivity and resistance patterns associated with TP-0903 by genomic, epigenomic, and transcriptomic profiling.
OUTLINE: This is a phase Ib, dose-escalation study of dubermatinib followed by a phase II study.
(FLT3 AML WITH RELAPSED/REFRACTORY DISEASE):
INDUCTION: Patients receive dubermatinib orally (PO) once daily (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.
After completion of study treatment, patients are followed up followed every 3 months for up to 2 years from registration and then every 6 months for up to 5 years from registration.
- Conditions
- Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Therapy-Related Acute Myeloid Leukemia
- Being tested
- Azacitidine, Dubermatinib
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given IV
DubermatinibDrug
Also called TP 0903, TP-0903, TP0903
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Azacitidine; Drug: Dubermatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of dubermatinib (TP-0903)
Determine a tolerable dose of TP-0903 monotherapy for relapsed/refractory patients with FLT3 AML.
Measured: 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.
Measured: 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.
Measured: through study completion, an average of 1 year
Secondary outcomes (6)
Disease-free survival
Will be summarized by the Kaplan-Meier method to determine disease-free survival for patients achieving complete response CR/CRh in each cohort of the study.
Measured: 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
The number of patients who got to transplant
Measured: Up to 5 years post registration
Overall survival
Will be summarized by the Kaplan-Meier method.
Measured: 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
Will be recorded for each patient and summarized.
Measured: Up to 5 years post registration
Incidence of treatment-related adverse events
Treatment-related adverse events, defined as possibly, probably or definitely related to study treatment per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 will be summarized separately.
Measured: Up to 5 years post registration
Tolerability of TP-0903
Reasons for treatment discontinuation and number of TP-0903 cycles received will be summarized and used to assess tolerability.
Measured: Up to 5 years post registration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2020
- Study start5 Nov 2020
- Primary completion13 Oct 2021
- Study completion22 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uma Borate
- Sponsor type
- University, hospital or other
- Collaborators
- Sumitomo Pharma America, Inc.
- Responsible party
- Sponsor-investigator, Uma Borate, Ohio State University Comprehensive Cancer Center
- Investigators
- Uma Borate, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04518345
- Sponsor's protocol ID
- OSU-19229
- Other IDs
- NCI-2020-04292
- Status last verified
- Feb 2023
- First submitted
- 30 Jul 2020
- Last updated
- 6 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of TP-0903 in Patients With Acute Myeloid Leukemia and FLT3 Mutations
- ClinicalTrials.gov ID
- NCT04518345
- Acronym / sponsor ID
- OSU-19229
- Conditions
- Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Therapy-Related Acute Myeloid Leukemia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Uma BorateUniversity, hospital or other
- Collaborators
- Sumitomo Pharma America, Inc.
- Study start
- 5 Nov 2020 (actual)
- Primary completion
- 13 Oct 2021 (actual)
- Study completion
- 22 Dec 2021 (actual)
- First posted
- 19 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To determine a tolerable dose of dubermatinib (TP-0903) monotherapy for relapsed/refractory patients with FLT3 acute myeloid leukemia (AML).
II. To determine the maximum tolerated dose (MTD) of TP-0903 with azacitidine in untreated unfit patients with FLT3 AML.
III. To determine the complete remission (CR) or complete remission with partial hematologic recovery (CRh) rate following induction therapy with TP-0903 in relapsed/refractory patients or TP-0903 with azacitidine therapy in untreated unfit patients with FLT3 AML.
SECONDARY OBJECTIVES:
- To determine the toxicity profile of TP-0903 as a single agent and in combination with or azacitidine.
II. To determine disease-free survival for patients achieving CR/CRh in each cohort.
III. To determine overall survival for patients in each cohort. IV. To determine the proportion of patients who go to transplant.
EXPLORATORY OBJECTIVES:
- To conduct pharmacokinetic studies of TP-0903 alone and in combination with azacitidine.
II. To examine changes in circulating AXL, Gas6, FLT3 ligand, and other cytokines/chemokines by TP-0903.
III. To determine the impact of TP-0903 on the inhibition of kinase signaling (AXL, FLT3, STAT5, AURKA), and metabolomics in AML cells.
IV. To determine differentially expressed genes in bone marrow stromal cells and AML cells upon TP-0903 treatment.
- To examine sensitivity and resistance patterns associated with TP-0903 by genomic, epigenomic, and transcriptomic profiling.
OUTLINE: This is a phase Ib, dose-escalation study of dubermatinib followed by a phase II study.
(FLT3 AML WITH RELAPSED/REFRACTORY DISEASE):
INDUCTION: Patients receive dubermatinib orally (PO) once daily (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.
After completion of study treatment, patients are followed up followed every 3 months for up to 2 years from registration and then every 6 months for up to 5 years from registration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (dubermatinib) | Experimental | Drug: Azacitidine, Drug: DubermatinibFLT3 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven IV | Drug | Treatment (dubermatinib) |
| DubermatinibAlso: TP 0903, TP-0903, TP0903Given PO | Drug | Treatment (dubermatinib) |
Primary outcome
Maximum tolerated dose of dubermatinib (TP-0903)
Time frame: Up to 28 days
Determine a tolerable dose of TP-0903 monotherapy for relapsed/refractory patients with FLT3 AML.
Composite complete response (CR) rate
Time frame: Up to 5 years post registration
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.
Composite CR rate with partial hematologic recovery (CRh) rate
Time frame: through study completion, an average of 1 year
Will calculate the composite CR rate (CR/CRh), defined according to the International Working Group criteria and assessed at the end of induction.
6 secondary outcomes
Disease-free survival
Time frame: 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
Time frame: Up to 5 years post registration
Overall survival
Time frame: 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
Time frame: Up to 5 years post registration
Incidence of treatment-related adverse events
Time frame: Up to 5 years post registration
Tolerability of TP-0903
Time frame: Up to 5 years post registration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Uma Borate, MD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Azacitidine and Dubermatinib in people with Acute Myeloid Leukemia and Secondary Acute Myeloid Leukemia, run by Uma Borate at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose of dubermatinib (TP-0903) (time frame: Up to 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.