Newly Diagnosed AML With FLT3 Activating MutationsPhase 2NCT02283177
A Safety and Tolerability Study of Crenolanib in Combination With Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia Patients With FLT3 Mutations
A Phase 2 study testing crenolanib, cytarabine and daunorubicin in people with Newly Diagnosed AML With FLT3 Activating Mutations, run by Arog Pharmaceuticals, Inc. at 9 sites in United States.
Trial summary
This pilot study is designed to evaluate the safety and tolerability of oral crenolanib besylate given sequentially during standard induction and consolidation chemotherapy in patients with newly diagnosed AML with FLT3 activating mutations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Newly Diagnosed AML With FLT3 Activating Mutations
- What is being tested?
- crenolanib, cytarabine and daunorubicin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 9 sitesUnited States
- Study dates
- Jan 2015to Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Unequivocal diagnosis of AML based on the WHO classification, excluding acute promyelocytic leukemia
- No prior therapy for AML, except for hydroxyurea, in this setting is allowed.
- Subjects with AML evolving from MDS may have received prior MDS therapy with demethylating agents
- Subjects must have tested positive for FLT3-ITD and/or other FLT3 activating mutations
- Age ≥18 years
- ECOG PS 0 - 2
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- Adequate liver function, defined as normal total bilirubin, ALT ≤2.0x ULN, and AST ≤2.0x ULN measured within 24 hours prior to crenolanib commencement
- Adequate renal function, defined as serum creatinine ≤1.5x ULN or GFR >50 mL/min
- Negative pregnancy test (serum or urine) for women of childbearing potential (WOCBP)
- Women considered not of childbearing potential include any of the following: no menses for at least 2 years or menses within 2 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months or with bilateral tubal ligation
- WOCBP must practice contraception. Acceptable methods of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, tubal ligations, and abstention
- Male patients (except those with prior surgical contraceptive procedures) with female partners who are of childbearing potential: Recommendation is for male and partner to use effective contraceptive methods, such as latex condoms, during the study
- Able and willing to provide written informed consent
Who cannot join
- Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)
- Active CNS leukemia
- Subject with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
- NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy
- Unable to swallow pills
- Major surgical procedures within 14 days of administration of crenolanib (does not include line placement as needed for chemotherapy administration).
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- Unwillingness or inability to comply with protocol.
- Concurrent use of other investigational agents.
- Subjects who are not eligible for standard chemotherapy
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
Cleveland Clinic
Cleveland, Ohio, 44195
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
City of Hope Medical Center
Duarte, California, 91010
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical College
New York, New York, 10065
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98195
About this study
Official title: A Safety and Tolerability Trial of Crenolanib and Chemotherapy With Cytarabine and Anthracyclines in Patients With Newly Diagnosed Acute Myeloid Leukemia With FLT3 Activating Mutations
This pilot study is designed to evaluate the safety and tolerability of oral crenolanib besylate given sequentially during standard induction and consolidation chemotherapy in patients with newly diagnosed AML with FLT3 activating mutations.
- Being tested
- crenolanib, cytarabine, daunorubicin, idarubicin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
crenolanibDrug
Also called CP-868,596-26
cytarabineDrug
daunorubicinDrug
idarubicinDrug
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Patients will be given cytarabine and daunorubicin during induction therapy plus crenolanib at 100 mg TID. Receives: Drug: crenolanib; Drug: cytarabine; Drug: daunorubicin |
| Cohort B | Experimental | Patients will be given cytarabine and idarubicin during induction therapy plus crenolanib at 100 mg TID. Receives: Drug: crenolanib; Drug: cytarabine; Drug: idarubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response to Crenolanib With Standard Induction Chemotherapy
To determine the response rate to crenolanib. Complete remission (CR) response criteria includes a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, the absence of Auer rods and extramedullary leukemia, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L. Complete remission with incomplete blood count recovery (CRi) response includes all CR criteria met, except participant do not achieve either platelet or ANC recovery. Composite Complete CR response includes all subjects who achieve a CR and CRi. Partial Response (PR) response includes all CR criteria met except a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline but within 5-25% or bone marrow blasts <5% with persistent Auer rods. Refractory Disease response includes subjects who do not satisfy the criteria for CR, CRi or PR.
Measured: 2 years
Secondary outcomes (1)
3-Year Overall Survival
Overall survival (OS) was measured from the date of the first dose of treatment to the date of death from any cause or to the last date that the patient was known to be alive. OS at 3-years is presented.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2014 (estimated)
- Study startJan 2015
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Newly Diagnosed AML With FLT3 Activating MutationsStudies 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arog Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard Stone, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02283177
- Sponsor's protocol ID
- ARO-006
- Status last verified
- Jan 2024
- First submitted
- 29 Oct 2014
- Last updated
- 2 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Wang ES, Goldberg AD, Tallman M, Walter RB, Karanes C, Sandhu K, Vigil CE, Collins R, Jain V, Stone RM. Crenolanib and Intensive Chemotherapy in Adults With Newly Diagnosed FLT3-Mutated AML. J Clin Oncol. 2024 May 20;42(15):1776-1787. doi: 10.1200/JCO.23.01061. Epub 2024 Feb 7.
PubMed 38324741
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Tolerability Trial of Crenolanib and Chemotherapy With Cytarabine and Anthracyclines in Patients With Newly Diagnosed Acute Myeloid Leukemia With FLT3 Activating Mutations
- ClinicalTrials.gov ID
- NCT02283177
- Acronym / sponsor ID
- ARO-006
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Arog Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2015
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 5 Nov 2014 (estimated)
- Results
- Posted 2 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot study is designed to evaluate the safety and tolerability of oral crenolanib besylate given sequentially during standard induction and consolidation chemotherapy in patients with newly diagnosed AML with FLT3 activating mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: crenolanib, Drug: cytarabine, Drug: daunorubicinPatients will be given cytarabine and daunorubicin during induction therapy plus crenolanib at 100 mg TID. |
| Cohort B | Experimental | Drug: crenolanib, Drug: cytarabine, Drug: idarubicinPatients will be given cytarabine and idarubicin during induction therapy plus crenolanib at 100 mg TID. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Unequivocal diagnosis of AML based on the WHO classification, excluding acute promyelocytic leukemia
- No prior therapy for AML, except for hydroxyurea, in this setting is allowed.
- Subjects with AML evolving from MDS may have received prior MDS therapy with demethylating agents
- Subjects must have tested positive for FLT3-ITD and/or other FLT3 activating mutations
- Age ≥18 years
Key exclusion criteria (9 listed)
- Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)
- Active CNS leukemia
- Subject with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
- NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy
- Unable to swallow pills
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 |
|---|---|---|
| crenolanibAlso: CP-868,596-26 | Drug | Cohort A, Cohort B |
| cytarabine | Drug | Cohort A, Cohort B |
| daunorubicin | Drug | Cohort A |
| idarubicin | Drug | Cohort B |
Primary outcome
Clinical Response to Crenolanib With Standard Induction Chemotherapy
Time frame: 2 years
To determine the response rate to crenolanib. Complete remission (CR) response criteria includes a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, the absence of Auer rods and extramedullary leukemia, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L. Complete remission with incomplete blood count recovery (CRi) response includes all CR criteria met, except participant do not achieve either platelet or ANC recovery. Composite Complete CR response includes all subjects who achieve a CR and CRi. Partial Response (PR) response includes all CR criteria met except a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline but within 5-25% or bone marrow blasts <5% with persistent Auer rods. Refractory Disease response includes subjects who do not satisfy the criteria for CR, CRi or PR.
1 secondary outcome
3-Year Overall Survival
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38324741Wang ES, Goldberg AD, Tallman M, Walter RB, Karanes C, Sandhu K, Vigil CE, Collins R, Jain V, Stone RM. Crenolanib and Intensive Chemotherapy in Adults With Newly Diagnosed FLT3-Mutated AML. J Clin Oncol. 2024 May 20;42(15):1776-1787. doi: 10.1200/JCO.23.01061. Epub 2024 Feb 7.
Related trials for Newly Diagnosed AML With FLT3 Activating Mutations
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ASTX727, Venetoclax, and Gilteritinib for the Treatment of Newly Diagnosed, Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Acute Myeloid Leukemia, 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.
Richard Stone, MD principal investigator
Dana-Farber Cancer Institute
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing crenolanib, cytarabine and daunorubicin in people with Newly Diagnosed AML With FLT3 Activating Mutations, run by Arog Pharmaceuticals, Inc. at 9 sites 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 13 inclusion and 9 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 2 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical Response to Crenolanib With Standard Induction Chemotherapy (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02283177, which also lists 1 linked publication.
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 2 Feb 2024.