Acute Myeloid Leukemia With FLT3 Activating Mutations That Has Relapsed or Been Refractory After One or More Prior TherapiesPhase 2NCT01657682
A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
A Phase 2 study testing Crenolanib besylate in people with Acute Myeloid Leukemia With FLT3 Activating Mutations That Has Relapsed or Been Refractory After One or More Prior Therapies, run by Arog Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
This pilot Phase II study is designed to evaluate the efficacy and tolerability of crenolanib in two cohorts of AML patients with FLT3 activation mutations (patients whose leukemia has recurred after prior chemotherapy not including a FLT3 TKI and patients whose leukemia has progressed after prior therapy with a FLT3… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia With FLT3 Activating Mutations That Has Relapsed or Been Refractory After One or More Prior Therapies
- What is being tested?
- Crenolanib besylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Apr 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
- Confirmed primary AML relapsed or refractory after prior therapy, AML secondary to antecedent chemotherapy or radiation therapy, or AML due to prior myelodysplastic syndrome (MDS)/ myeloproliferative neoplasm (MPN) as defined by WHO criteria with presence of either FLT3 ITD and/or other FLT3 activating mutations
- Patients with secondary AML should have failed no more than two (2) prior regimens
- Patients with antecedent MDS/MPN, defined by WHO criteria, without any prior therapy for AML, regardless of the number of therapies for MDS/ MPN
- Patients with primary AML should have received no more than two (2) prior cytotoxic containing salvage regimens. Reinduction with the same regimen or stem cell transplant will not be considered a separate salvage regimen. Change of drugs will be considered a salvage regimen. Unlimited FLT3 TKI therapy (even in combination with cytotoxics/hypomethylating agents) is allowed for patients enrolled in cohort B
- Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within 30 day screening period
- Males and females age ≥18 years
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- ECOG PS 0-2
- Adequate liver function, defined as bilirubin ≤1.5x ULN, ALT ≤3.0x ULN, and AST ≤3.0x ULN
- Adequate renal function, defined as serum creatinine ≤1.5x ULN
- Recovery from non-hematological toxicities of prior therapy (including HSCT) to no more than grade 1 (except alopecia)
- Subjects should have received no anti-leukemic therapy (except hydroxyurea) prior to the first dose of crenolanib as follows: for 14 days for classical cytotoxic agents and for five times the t1/2 (half-life) for FLT3 inhibitors and antineoplastic agents that are neither cytotoxic nor FLT3 inhibitors (e.g. hypomethylating agent or MEK inhibitor)
- Negative pregnancy test for WOCBP
- Able and willing to provide written informed consent.
Who cannot join
- Absence of a FLT3 activating mutation
- <5% blasts in blood or marrow at screening
- Concurrent chemotherapy, or targeted anti-cancer agents, other than hydroxyurea
- Patient 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
- HIV infection or active hepatitis B (defined as hepatitis B surface antigen positive) or C (defined as hepatitis C antibody positive)
- Known clinically active central nervous system (CNS) leukemia
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- Patients less than 30 days post HSCT
- Subjects who have clinically significant graft versus host disease requiring treatment and /or have >grade 2 persistent non hematological toxicity related to transplant
- Prior crenolanib treatment for a non-leukemic indication
- Major surgical procedures within 14 days of Day 1 administration of crenolanib.
- Unwillingness or inability to comply with protocol.
Trial locations and contacts
1 site in 1 country.
About this study
This pilot Phase II study is designed to evaluate the efficacy and tolerability of crenolanib in two cohorts of AML patients with FLT3 activation mutations (patients whose leukemia has recurred after prior chemotherapy not including a FLT3 TKI and patients whose leukemia has progressed after prior therapy with a FLT3 TKI).
Read the detailed description
This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed acute myeloid leukemia (AML) with FLT3 activating mutations. Two cohorts of patients will be enrolled: those whose AML has recurred after prior chemotherapy without a FLT3 TKI, and those whose AML has progressed after prior therapy with FLT3 TKIs. Subjects will take Crenolanib besylate at 100 mg TID until disease progression, death, or unacceptable toxicities. Concurrent hydroxyurea is permitted during the first 28 days of study therapy.
- Being tested
- Crenolanib besylate
- Keywords
- FLT3, Crenolanib, Acute, Myeloid, AML
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crenolanib besylateDrug
Crenolanib besylate, 100 mg TID, taken orally at least 30 minutes pre- or post- meal. Patients will complete a daily diary to record the date, time and amount (number of tablets) of crenolanib taken and eating schedule.
Concurrent hydroxyurea (maximum 5g total daily dose x 14 days) is permitted during the first 28 days of study therapy.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A - No prior FLT3 TKI exposure | Experimental | Will enroll relapsed/refractory AML patients with FLT3 activating mutations who progressed on one or more prior chemotherapy regimens excluding any FLT3 TKI. Receives: Drug: Crenolanib besylate |
| Cohort B - Prior therapy with FLT3 TKI | Experimental | Will enroll relapsed/refractory AML patients with FLT3 activating mutations whose leukemia has progressed and have history of prior therapy with one or more FLT3 TKIs. Receives: Drug: Crenolanib besylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate of Patients Receiving Crenolanib Therapy
To determine the response rate to crenolanib. CR Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Partial Response (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Blast reduction (BR) response included a decrease of ≥50% in % blasts. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS.
Measured: From the date of first dose to the end of protocol treatment.
Secondary outcomes (2)
Duration of Overall Survival
To determine the overall survival of AML patients with activating FLT3 mutations treated with crenolanib
Measured: From the date of first dose up to end of treatment, up to 24 months.
Study Drug Exposure
To determine the study drug exposure of relapse/refractory AML patients receiving 100 mg crenolanib besylate tablets three times daily.
Measured: Defined as the duration from first day to the last dose, up to 24 months, interruptions in study drug administration were not counted.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2012 (estimated)
- Study startOct 2012
- Primary completionApr 2019
- Study completionApr 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 Acute Myeloid Leukemia With FLT3 Activating Mutations That Has Relapsed or Been Refractory After One or More Prior TherapiesStudies 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
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arog Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jorge Cortes, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01657682
- Sponsor's protocol ID
- ARO-005
- Status last verified
- Nov 2023
- First submitted
- 31 Jul 2012
- Last updated
- 30 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Galanis A, Ma H, Rajkhowa T, Ramachandran A, Small D, Cortes J, Levis M. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood. 2014 Jan 2;123(1):94-100. doi: 10.1182/blood-2013-10-529313. Epub 2013 Nov 13.
PubMed 24227820
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
- ClinicalTrials.gov ID
- NCT01657682
- Acronym / sponsor ID
- ARO-005
- Keywords
- FLT3, Crenolanib, Acute, Myeloid, AML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Arog Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- Apr 2019 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 6 Aug 2012 (estimated)
- Results
- Posted 30 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot Phase II study is designed to evaluate the efficacy and tolerability of crenolanib in two cohorts of AML patients with FLT3 activation mutations (patients whose leukemia has recurred after prior chemotherapy not including a FLT3 TKI and patients whose leukemia has progressed after prior therapy with a FLT3 TKI).
Detailed description
This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed acute myeloid leukemia (AML) with FLT3 activating mutations. Two cohorts of patients will be enrolled: those whose AML has recurred after prior chemotherapy without a FLT3 TKI, and those whose AML has progressed after prior therapy with FLT3 TKIs. Subjects will take Crenolanib besylate at 100 mg TID until disease progression, death, or unacceptable toxicities. Concurrent hydroxyurea is permitted during the first 28 days of study therapy.
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 - No prior FLT3 TKI exposure | Experimental | Drug: Crenolanib besylateWill enroll relapsed/refractory AML patients with FLT3 activating mutations who progressed on one or more prior chemotherapy regimens excluding any FLT3 TKI. |
| Cohort B - Prior therapy with FLT3 TKI | Experimental | Drug: Crenolanib besylateWill enroll relapsed/refractory AML patients with FLT3 activating mutations whose leukemia has progressed and have history of prior therapy with one or more FLT3 TKIs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Confirmed primary AML relapsed or refractory after prior therapy, AML secondary to antecedent chemotherapy or radiation therapy, or AML due to prior myelodysplastic syndrome (MDS)/ myeloproliferative neoplasm (MPN) as defined by WHO criteria with presence of either FLT3 ITD and/or other FLT3 activating mutations
- Patients with secondary AML should have failed no more than two (2) prior regimens
- Patients with antecedent MDS/MPN, defined by WHO criteria, without any prior therapy for AML, regardless of the number of therapies for MDS/ MPN
- Patients with primary AML should have received no more than two (2) prior cytotoxic containing salvage regimens. Reinduction with the same regimen or stem cell transplant will not be considered a separate salvage regimen. Change of drugs will be considered a salvage regimen. Unlimited FLT3 TKI therapy (even in combination with cytotoxics/hypomethylating agents) is allowed for patients enrolled in cohort B
- Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within 30 day screening period
Key exclusion criteria (11 listed)
- Absence of a FLT3 activating mutation
- <5% blasts in blood or marrow at screening
- Concurrent chemotherapy, or targeted anti-cancer agents, other than hydroxyurea
- Patient 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
- HIV infection or active hepatitis B (defined as hepatitis B surface antigen positive) or C (defined as hepatitis C antibody positive)
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 |
|---|---|---|
| Crenolanib besylateCrenolanib besylate, 100 mg TID, taken orally at least 30 minutes pre- or post- meal. Patients will complete a daily diary to record the date, time and amount (number of tablets) of crenolanib taken and eating schedule. Concurrent hydroxyurea (maximum 5g total daily dose x 14 days) is permitted during the first 28 days of study therapy. | Drug | Cohort A - No prior FLT3 TKI exposure, Cohort B - Prior therapy with FLT3 TKI |
Primary outcome
Response Rate of Patients Receiving Crenolanib Therapy
Time frame: From the date of first dose to the end of protocol treatment.
To determine the response rate to crenolanib. CR Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Partial Response (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Blast reduction (BR) response included a decrease of ≥50% in % blasts. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS.
2 secondary outcomes
Duration of Overall Survival
Time frame: From the date of first dose up to end of treatment, up to 24 months.
Study Drug Exposure
Time frame: Defined as the duration from first day to the last dose, up to 24 months, interruptions in study drug administration were not counted.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24227820Galanis A, Ma H, Rajkhowa T, Ramachandran A, Small D, Cortes J, Levis M. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood. 2014 Jan 2;123(1):94-100. doi: 10.1182/blood-2013-10-529313. Epub 2013 Nov 13.
- AROG PharmaceuticalsLink provided by the sponsor.
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.
Jorge Cortes, MD principal investigator
M.D. Anderson Cancer Center
1 site 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 besylate in people with Acute Myeloid Leukemia With FLT3 Activating Mutations That Has Relapsed or Been Refractory After One or More Prior Therapies, run by Arog Pharmaceuticals, Inc. 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 13 inclusion and 11 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 30 Nov 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?
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 30 Nov 2023). 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?
Response Rate of Patients Receiving Crenolanib Therapy (time frame: From the date of first dose to the end of protocol treatment.). 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 NCT01657682, 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 30 Nov 2023.