Acute Myeloid LeukemiaPhase 1/2NCT02400281
Study of Crenolanib Combined With Chemotherapy in FLT3-mutated Acute Myeloid Leukemia Patients
A Phase 1/2 study testing Crenolanib besylate, Idarubicin and Cytarabine in people with Acute Myeloid Leukemia, run by Arog Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
This is an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Crenolanib besylate, Idarubicin and Cytarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to 15 Jul 2020
- Phase
- Phase 1/2
- 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 diagnosis of refractory/relapsed AML or high-risk MDS
- Arm 1: Subjects must have received at least one prior therapy and a maximum of three prior therapies
- Arm 2: Subjects must have received at least one prior therapy and a maximum of three prior therapies. No prior treatment with 5-Azacitidine is allowed in this arm.
- FLT3 mutation positive (ITD, TKD or other)
- ECOG PS 0-2
- Adequate liver and renal function
- Negative pregnancy test
- Extramedullary leukemia allowed except CNS disease
Who cannot join
- Arm 1 and 2 Exclusion:
- <5% blasts in marrow or blood at time of screening
- Active HIV, hepatitis B or C
- CNS leukemia
- Clinically significant GVHD or organ dysfunction where chemotherapy specified by protocol cannot be given
- Patient with AML-M3 (APL)
- Pre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I-II Study of Crenolanib Combined With Standard Salvage Chemotherapy, and Crenolanib Combined With 5-Azacitidine in Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
This is an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine
Read the detailed description
For each arm:
The phase I with dose-limiting toxicity (DLT) determination will use 3+3 design.
Phase II total of 52 patients (26 per arm) will be treated at established phase I dose.
Enrollment to be simultaneous to each arm.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Crenolanib besylate, Idarubicin, Cytarabine, Azacytidine, Mitoxantrone
- 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.
Crenolanib besylateDrug
Also called CP-868,596-26
IdarubicinDrug
Also called 4-demethoxydaunorubicin
CytarabineDrug
Also called cytosine arabinoside
AzacytidineDrug
Also called 5-azacytidine
MitoxantroneDrug
Also called Novantrone
EtoposideDrug
Also called etoposide phosphate
FludarabineDrug
Also called Fludarabine phosphate
G-CSFDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 crenolanib besylate combination | Experimental | Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin Receives: Drug: Crenolanib besylate; Drug: Idarubicin; Drug: Cytarabine; Drug: Mitoxantrone; Drug: Etoposide; Drug: Fludarabine; Drug: G-CSF |
| Arm 2 crenolanib besylate combination | Experimental | Arm 2 patients will receive crenolanib besylate and azacytidine. Receives: Drug: Crenolanib besylate; Drug: Azacytidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate of Crenolanib Besylate Combination 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. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS. Death in aplasia response include deaths occurring following chemotherapy while cytopenic with an aplastic or hypoplastic BM prior to death without evidence of persistent leukemia.
Measured: Baseline up to first documented response, persistent disease, or death (whichever occurs first), 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2015 (estimated)
- Study startSep 2015
- Primary completion15 Jul 2020
- Study completion15 Jul 2020
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 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 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
- NCT02400281
- Sponsor's protocol ID
- ARO-010
- Status last verified
- Jun 2024
- First submitted
- 18 Mar 2015
- Last updated
- 3 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Study of Crenolanib Combined With Standard Salvage Chemotherapy, and Crenolanib Combined With 5-Azacitidine in Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
- ClinicalTrials.gov ID
- NCT02400281
- Acronym / sponsor ID
- ARO-010
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Arog Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2015
- Primary completion
- 15 Jul 2020 (actual)
- Study completion
- 15 Jul 2020 (actual)
- First posted
- 27 Mar 2015 (estimated)
- Results
- Posted 20 Mar 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 an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine
Detailed description
For each arm:
The phase I with dose-limiting toxicity (DLT) determination will use 3+3 design.
Phase II total of 52 patients (26 per arm) will be treated at established phase I dose.
Enrollment to be simultaneous to each arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 crenolanib besylate combination | Experimental | Drug: Crenolanib besylate, Drug: Idarubicin, Drug: Cytarabine, Drug: Mitoxantrone, Drug: Etoposide, Drug: Fludarabine, Drug: G-CSFArm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin |
| Arm 2 crenolanib besylate combination | Experimental | Drug: Crenolanib besylate, Drug: AzacytidineArm 2 patients will receive crenolanib besylate and azacytidine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Confirmed diagnosis of refractory/relapsed AML or high-risk MDS
- FLT3 mutation positive (ITD, TKD or other)
- ECOG PS 0-2
- Adequate liver and renal function
- Negative pregnancy test
Key exclusion criteria (7 listed)
- Arm 1 and 2 Exclusion:
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 besylateAlso: CP-868,596-26 | Drug | Arm 1 crenolanib besylate combination, Arm 2 crenolanib besylate combination |
| IdarubicinAlso: 4-demethoxydaunorubicin | Drug | Arm 1 crenolanib besylate combination |
| CytarabineAlso: cytosine arabinoside | Drug | Arm 1 crenolanib besylate combination |
| AzacytidineAlso: 5-azacytidine | Drug | Arm 2 crenolanib besylate combination |
| MitoxantroneAlso: Novantrone | Drug | Arm 1 crenolanib besylate combination |
| EtoposideAlso: etoposide phosphate | Drug | Arm 1 crenolanib besylate combination |
| FludarabineAlso: Fludarabine phosphate | Drug | Arm 1 crenolanib besylate combination |
| G-CSF | Drug | Arm 1 crenolanib besylate combination |
Primary outcome
Response Rate of Crenolanib Besylate Combination Therapy
Time frame: Baseline up to first documented response, persistent disease, or death (whichever occurs first), 1 year.
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. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS. Death in aplasia response include deaths occurring following chemotherapy while cytopenic with an aplastic or hypoplastic BM prior to death without evidence of persistent leukemia.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
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 1/2 study testing Crenolanib besylate, Idarubicin and Cytarabine in people with Acute Myeloid Leukemia, 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 8 inclusion and 7 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 3 Jul 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 20 Mar 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?
Response Rate of Crenolanib Besylate Combination Therapy (time frame: Baseline up to first documented response, persistent disease, or death (whichever occurs first), 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 3 Jul 2024.