Relapsed/Refractory Acute Myeloid Leukemia (AML)Phase 1/2NCT02626338
Pilot Study of Crenolanib Combined With Standard Salvage Chemotherapy in Subjects With R/R AML
A Phase 1/2 study testing Crenolanib, Mitoxantrone and Cytarabine in people with Relapsed/Refractory Acute Myeloid Leukemia (AML), run by Arog Pharmaceuticals, Inc. at 4 sites in United States.
Trial summary
The proposed study is designed to combine crenolanib with standard salvage chemotherapy to treat patients with R/R AML irrespective the FLT3 status. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Acute Myeloid Leukemia (AML)
- What is being tested?
- Crenolanib, Mitoxantrone and Cytarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2016to Feb 2018
- 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 AML, including treatment-related secondary AML (except prior MDS) according to World Health Organization (WHO) 2008 classification at treating institution
- Subjects who are refractory* or who have relapsed** following first line AML therapy with cytarabine/anthracycline based chemotherapy, with or without a tyrosine kinase inhibitor. *Refractory to induction therapy is defined as never achieving CR, CRi or CRp (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI.
- or
- First relapse is defined as untreated hematologic relapse (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI that induced a CR/CRi/CRp. Subjects are allowed to receive induction, consolidation, transplant and/or maintenance prior to achieving their first CR/CRi/CRp.
- Subjects considered eligible for intensive chemotherapy
- ECOG performance status ≤ 2
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- Age ≥ 18 years
- Adequate liver function within 72 hours of enrollment, defined as:
- Normal total serum bilirubin
- ALT and AST ≤ 2.0 x ULN
- Adequate renal function, defined as serum creatinine ≤ 1.5x ULN
- Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 72 hours prior to enrollment "Woman of childbearing potential" is defined as any woman who has not undergone a hysterectomy and who has had menses at any time in the preceding 24 consecutive months
- Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy) while on crenolanib and for 3 months following the last dose of crenolanib. Hormonal contraception alone is not an acceptable method of birth control for the purpose of this trial.
- Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 3 month after the last dose of crenolanib).
- Willing to adhere to protocol specific requirements 12. Following receipt of verbal and written information about the study, the subject must provide signed informed consent before any study related activity is carried out. 13. Clinically significant toxic effects of prior therapy (expect hydroxyuria) resolved to Grade ≤ 1 before the start of study.
Who cannot join
- < 5% blasts in blood or marrow at screening, except if measurable extramedullary AML is confirmed
- Acute promyelocytic leukemia (APL)
- Known clinically active CNS leukemia
- Clinically active or unstable graft-versus-host disease (GvHD) requiring treatment which precludes administration of chemotherapy as defined in this protocol
- Prior anti-leukemia therapy within 14 days of enrollment for classical cytotoxic agents, and within 5x the half-life for other investigational agents
- Prior use of hydroxyurea or isolated doses of cytarabine for palliation (i.e., control of WBC) are allowed but should be discontinued at least 24 hrs prior to enrollment.
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- Other agents used strictly with palliative intent might be allowed during this period after discussing with principal investigator
- Pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
- Known HIV infection.
- Evidence of ongoing, uncontrolled systemic infection or an uncontrolled local infection requiring therapy at the start of study.
- "Currently active" second malignancy (other than non-melanoma skin cancer, carcinoma in situ of the cervix or prostatic intraepithelial neoplasia within 1 year). Subjects are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within 1 year.
- Concurrent participation in another therapeutic clinical trial.
- Pregnant or breastfeeding women
- Subjects of childbearing potential not willing to use adequate contraception during study and 3 months after last dose of crenolanib
- Subject with uncontrolled cardiac disease including congestive heart failure class III or IV by the NYHA, unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
- Subject with concurrent severe and/or uncontrolled medical or psychiatric conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
- Inability to give an informed consent
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
City of Hope Medical Center
Duarte, California, 91010
Houston Methodist
Houston, Texas, 77030
University of Arkansas
Little Rock, Arkansas, 72205
About this study
Official title: Pilot Study of Crenolanib Combined With Standard Salvage Chmetherapy in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
The proposed study is designed to combine crenolanib with standard salvage chemotherapy to treat patients with R/R AML irrespective the FLT3 status.
Read the detailed description
Open label, dose de-escalation, pilot trial of crenolanib with standard salvage chemotherapy. Subjects may receive up to 2 cycles of induction with standard salvage chemotherapy followed by crenolanib. Each arm will enroll approximately 24 patients (72 total); stratification to each arm will be per physician's choice
- Being tested
- Crenolanib, Mitoxantrone, Cytarabine, Etoposide, Fludarabine
- 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.
CrenolanibDrug
MitoxantroneDrug
CytarabineDrug
Also called cytosine arabinoside
EtoposideDrug
Also called Etoposide phosphate
FludarabineDrug
Also called Fludarabine monophosphate
G-CSFDrug
IdarubicinDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | * Mitoxantrone
* Cytarabine
* Crenolanib Receives: Drug: Crenolanib; Drug: Mitoxantrone; Drug: Cytarabine |
| Arm B | Experimental | * Fludarabine
* Cytarabine
* G-CSF
* Idarubicin
* Crenolanib Receives: Drug: Crenolanib; Drug: Cytarabine; Drug: Fludarabine; Drug: G-CSF; Drug: Idarubicin |
| Arm C | Experimental | * Mitoxantrone
* Etoposide
* Cytarabine
* Crenolanib Receives: Drug: Crenolanib; Drug: Mitoxantrone; Drug: Cytarabine; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response to Crenolanib With Standard Salvage Chemotherapy
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 have either platelet recovery or ANC recovery. CRh response included all CR criteria met, except subject only has partial platelet recovery and ANC recovery. Complete CR (CRc) response includes all subjects who achieve a CR, CRi and CRh. Partial Response (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline but >5%. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2015 (estimated)
- Study startFeb 2016
- Primary completionFeb 2018
- Study completionFeb 2018
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/Refractory Acute Myeloid Leukemia (AML)Studies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 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
- NCT02626338
- Sponsor's protocol ID
- ARO-011
- Status last verified
- Dec 2023
- First submitted
- 18 Nov 2015
- Last updated
- 20 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Crenolanib Combined With Standard Salvage Chmetherapy in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT02626338
- Acronym / sponsor ID
- ARO-011
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Arog Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2016 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 10 Dec 2015 (estimated)
- Results
- Posted 20 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is designed to combine crenolanib with standard salvage chemotherapy to treat patients with R/R AML irrespective the FLT3 status.
Detailed description
Open label, dose de-escalation, pilot trial of crenolanib with standard salvage chemotherapy. Subjects may receive up to 2 cycles of induction with standard salvage chemotherapy followed by crenolanib. Each arm will enroll approximately 24 patients (72 total); stratification to each arm will be per physician's choice
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Crenolanib, Drug: Mitoxantrone, Drug: Cytarabine* Mitoxantrone * Cytarabine * Crenolanib |
| Arm B | Experimental | Drug: Crenolanib, Drug: Cytarabine, Drug: Fludarabine, Drug: G-CSF, Drug: Idarubicin* Fludarabine * Cytarabine * G-CSF * Idarubicin * Crenolanib |
| Arm C | Experimental | Drug: Crenolanib, Drug: Mitoxantrone, Drug: Cytarabine, Drug: Etoposide* Mitoxantrone * Etoposide * Cytarabine * Crenolanib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Confirmed diagnosis of AML, including treatment-related secondary AML (except prior MDS) according to World Health Organization (WHO) 2008 classification at treating institution
- Subjects who are refractory* or who have relapsed** following first line AML therapy with cytarabine/anthracycline based chemotherapy, with or without a tyrosine kinase inhibitor. *Refractory to induction therapy is defined as never achieving CR, CRi or CRp (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI.
- or
- First relapse is defined as untreated hematologic relapse (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI that induced a CR/CRi/CRp. Subjects are allowed to receive induction, consolidation, transplant and/or maintenance prior to achieving their first CR/CRi/CRp.
- Subjects considered eligible for intensive chemotherapy
Key exclusion criteria (17 listed)
- < 5% blasts in blood or marrow at screening, except if measurable extramedullary AML is confirmed
- Acute promyelocytic leukemia (APL)
- Known clinically active CNS leukemia
- Clinically active or unstable graft-versus-host disease (GvHD) requiring treatment which precludes administration of chemotherapy as defined in this protocol
- Prior anti-leukemia therapy within 14 days of enrollment for classical cytotoxic agents, and within 5x the half-life for other investigational agents
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 | Drug | Arm A, Arm B, Arm C |
| Mitoxantrone | Drug | Arm A, Arm C |
| CytarabineAlso: cytosine arabinoside | Drug | Arm A, Arm B, Arm C |
| EtoposideAlso: Etoposide phosphate | Drug | Arm C |
| FludarabineAlso: Fludarabine monophosphate | Drug | Arm B |
| G-CSF | Drug | Arm B |
| Idarubicin | Drug | Arm B |
Primary outcome
Clinical Response to Crenolanib With Standard Salvage Chemotherapy
Time frame: 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 have either platelet recovery or ANC recovery. CRh response included all CR criteria met, except subject only has partial platelet recovery and ANC recovery. Complete CR (CRc) response includes all subjects who achieve a CR, CRi and CRh. Partial Response (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline but >5%. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites 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, Mitoxantrone and Cytarabine in people with Relapsed/Refractory Acute Myeloid Leukemia (AML), run by Arog Pharmaceuticals, Inc. at 4 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 15 inclusion and 17 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 20 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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 Dec 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?
Clinical Response to Crenolanib With Standard Salvage Chemotherapy (time frame: 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 20 Dec 2023.