Relapsed or Refractory Acute Myeloid Leukemia With FLT3 Activating MutationsPhase 2NCT01522469
Phase II Study of Crenolanib in Subjects With Relapsed/Refractory AML With FLT3 Activating Mutations
A Phase 2 study testing Crenolanib Besylate (CP-868,596-26) in people with Relapsed or Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations, run by Arog Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed or refractory AML with FLT3 activating mutations. Prior treatment with other FLT3 TKIs is allowed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations
- What is being tested?
- Crenolanib Besylate (CP-868,596-26)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Nov 2014
- 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
- Relapsed/refractory primary AML or AML secondary to antecedent hematologic disorder with an expected survival of 3 months or greater
- Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within < 60 days of the screening period.
- Age ≥18 years
- ECOG PS 0 - 2
- Adequate liver function, defined as total or direct bilirubin ≤1.5x ULN, ALT ≤3.0x ULN,AST ≤3.0x ULN. Exceptions for ALT and AST restrictions will be made in the setting of documented liver involvement with leukemia
- Adequate renal function, defined as serum creatinine ≤1.5x ULN
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- 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 women of childbearing potential
- Able and willing to provide written informed consent
- Subjects who received crenolanib prior to and are within 30-90 days of an allogeneic stem cell transplant (HSCT) and have either no active GVHD where therapy has been initiated or GVHD where therapy has not been escalated within 14 days prior to start of study drug
Who cannot join
- Absence of FLT3 activating mutation
- <5% blasts in blood or marrow at screening
- Concurrent chemotherapy, systemic immunosuppressants, 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 manifested as hepatitis surface antigen positive (HepBsAg) or hepatitis C manifested as hepatitis C antibody positive
- For post HSCT, subjects who are within 29 days of an allogeneic transplant, and/or are on an unstable dose of immunosuppressive drugs for management or prophylaxis of GVHD or have escalated therapy for GVHD within 14 days of starting study drug and/or have >/=Grade 2 persistent non hematological toxicity related to the transplant or did not receive crenolanib prior to HSCT
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- Evidence of lack of engraftment if post allogeneic transplant
- Unable to swallow pills
- Major surgical procedures within 14 days of Cycle 1 Day 1 administration of crenolanib
- Unwillingness or inability to comply with protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: A Phase II Study of Crenolanib Besylate in Subjects With Relapsed/Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations
This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed or refractory AML with FLT3 activating mutations. Prior treatment with other FLT3 TKIs is allowed. Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission.
- Being tested
- Crenolanib Besylate (CP-868,596-26)
- Keywords
- FLT3, Crenolanib, Acute, myeloid, leukemia, relapsed, refractory
- Medical subject headings
- Recurrence, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crenolanib Besylate (CP-868,596-26)Drug
Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission.
| Study group | Role | What they receive |
|---|---|---|
| Crenolanib Besylate | Experimental | Not described Receives: Drug: Crenolanib Besylate (CP-868,596-26) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
To determine the response rate to crenolanib.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 but >5%. Hematologic improvement (HI) response included erythroid response where Hgb increased ≥ 1.5 g/dL, platelet response where platelets increased ≥ 30 x 10^9/L for patient starting with >20 x 10^9/L platelets or increase from <20 x 10^9/L to >20 x 10^9/L and by at least 100% and neutrophil response where at least 100% increase and an increase >0.5 x 10^9/L. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or HI.
Measured: From the date of first dose to the end of protocol treatment, 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2012 (estimated)
- Study startJul 2012
- Primary completionAug 2014
- Study completionNov 2014
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.
- Other trials for Relapsed or Refractory Acute Myeloid Leukemia 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arog Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01522469
- Sponsor's protocol ID
- ARO-004
- Status last verified
- Jan 2024
- First submitted
- 30 Jan 2012
- Last updated
- 30 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Crenolanib Besylate in Subjects With Relapsed/Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations
- ClinicalTrials.gov ID
- NCT01522469
- Acronym / sponsor ID
- ARO-004
- Keywords
- FLT3, Crenolanib, Acute, myeloid, leukemia, relapsed, refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Arog Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 31 Jan 2012 (estimated)
- Results
- Posted 30 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed or refractory AML with FLT3 activating mutations. Prior treatment with other FLT3 TKIs is allowed. Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Crenolanib Besylate | Experimental | Drug: Crenolanib Besylate (CP-868,596-26) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Relapsed/refractory primary AML or AML secondary to antecedent hematologic disorder with an expected survival of 3 months or greater
- Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within < 60 days of the screening period.
- Age ≥18 years
- ECOG PS 0 - 2
- Adequate liver function, defined as total or direct bilirubin ≤1.5x ULN, ALT ≤3.0x ULN,AST ≤3.0x ULN. Exceptions for ALT and AST restrictions will be made in the setting of documented liver involvement with leukemia
Key exclusion criteria (10 listed)
- Absence of FLT3 activating mutation
- <5% blasts in blood or marrow at screening
- Concurrent chemotherapy, systemic immunosuppressants, 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 manifested as hepatitis surface antigen positive (HepBsAg) or hepatitis C manifested 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 Besylate (CP-868,596-26)Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission. | Drug | Crenolanib Besylate |
Primary outcome
Overall Response Rate
Time frame: From the date of first dose to the end of protocol treatment, 1 year.
To determine the response rate to crenolanib.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 but >5%. Hematologic improvement (HI) response included erythroid response where Hgb increased ≥ 1.5 g/dL, platelet response where platelets increased ≥ 30 x 10^9/L for patient starting with >20 x 10^9/L platelets or increase from <20 x 10^9/L to >20 x 10^9/L and by at least 100% and neutrophil response where at least 100% increase and an increase >0.5 x 10^9/L. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or HI.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AROG Pharmaceuticals, LLCLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 (CP-868,596-26) in people with Relapsed or Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations, 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 11 inclusion and 10 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 Jan 2024. 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 Jan 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?
Overall Response Rate (time frame: From the date of first dose to the end of protocol treatment, 1 year.). 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 30 Jan 2024.