Relapsed/Refractory FLT3-mutated AMLPhase 2NCT03324243
A Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
A Phase 2 study testing Crenolanib, Fludarabine and Cytarabine in people with Relapsed/Refractory FLT3-mutated AML, run by Arog Pharmaceuticals, Inc..
Trial summary
This is a phase II, multicenter, single-arm study to assess the safety and feasibility of combining crenolanib with fludarabine and cytarabine chemotherapy in pediatric patients with relapsed/refractory FLT3-mutated AML. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Relapsed/Refractory FLT3-mutated AML
- What is being tested?
- Crenolanib, Fludarabine and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2018to Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 1 years and ≤ 21 years
- Confirmed diagnosis of AML according to World Health Organization (WHO) 2016 classification
- Definitive evidence of a FLT3-ITD and/or FLT3-TKD (D835/I836) mutation at the time of enrollment
- Patients must have histologically or molecularly confirmed relapsed or refractory AML
- Karnofsky or Lansky performance score ≥ 50. Use Karnofsky for patients > 16 years old and Lansky for patients ≤ 16 years of age.
- Adequate renal function, defined as:
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- Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or
- Normal serum creatinine based on age/gender
- Adequate liver function, defined as:
- Serum total bilirubin ≤ 1.5x ULN for age,
- Serum aspartate aminotransferase (AST) ≤ 3.0x ULN for age, and
- Serum alanine aminotransferase (ALT) ≤ 3.0x ULN for age.
Who cannot join
- Patients with any of the following current or previous diagnoses:
- Acute promyelocytic leukemia (APL)
- Down syndrome
- DNA fragility or bone marrow failure syndromes (such as Fanconi anemia, Bloom syndrome, Kostmann syndrome, or Shwachman syndrome)
- AML secondary to prior MDS/MPN, including chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia
- Blastic plasmacytoid dendritic cell neoplasm
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- Acute leukemia of ambiguous lineage
- B-lymphoblastic leukemia/lymphoma
- T-lymphoblastic leukemia/lymphoma, including early T-cell precursor lymphoblastic leukemia (ETP-ALL)
- Patients who are refractory to first line (induction and re-induction) and a second line (1st salvage) treatment for AML.
- Patients who have received more than 1 prior allogeneic HSCT
- Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection of which they exhibit ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
- Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
- Known severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis or hyperbilirubinemia)
- Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Currently receiving prophylactic treatment of hepatitis B with anti-viral therapy
- Known infection with human immunodeficiency virus (HIV)
About this study
Official title: A Phase II Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
This is a phase II, multicenter, single-arm study to assess the safety and feasibility of combining crenolanib with fludarabine and cytarabine chemotherapy in pediatric patients with relapsed/refractory FLT3-mutated AML. Patients will receive up to two courses of salvage chemotherapy with fludarabine, cytarabine, and crenolanib. Response will be assessed between day 29-43 of each course.
- Conditions
- Relapsed/Refractory FLT3-mutated AML
- Being tested
- Crenolanib, Fludarabine, Cytarabine
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CrenolanibDrug
Also called Crenolanib besylate
66.7 mg/m2 three times a day (TID)
FludarabineDrug
30 mg/m2/day, intravenous infusions over 30 mins.
CytarabineDrug
2000 mg/m2/day, intravenous infusions over 1-3 hours.
| Study group | Role | What they receive |
|---|---|---|
| Crenolanib | Experimental | Not described Receives: Drug: Crenolanib; Drug: Fludarabine; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0
Measured: From study entry to 30 days post-treatment
Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0
Measured: 60 days
Rate of early mortality
Number of patients who died within 60 days of start of therapy
Measured: 60 days
Secondary outcomes (3)
Event-free survival (EFS)
EFS is defined as the time from the date of start of treatment to the date of failure to achieve a remission, relapse, or death from any cause.
Measured: 4 years
Relapse-free survival (RFS)
RFS is defined as the time from the date of remission to date of relapse or death.
Measured: 4 years
Overall survival (OS)
OS is defined as the time from the date of start of treatment until death.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study startJan 2018 (estimated)
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: Withdrawn: Study halted prior to enrollment of first participant
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory FLT3-mutated AMLStudies 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
- 0 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
- NCT03324243
- Sponsor's protocol ID
- ARO-014
- Status last verified
- Jan 2019
- First submitted
- 18 Oct 2017
- Last updated
- 10 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03324243
- Acronym / sponsor ID
- ARO-014
- Conditions
- Relapsed/Refractory FLT3-mutated AML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn: Study halted prior to enrollment of first participant
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Arog Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2018 (estimated)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 27 Oct 2017 (actual)
- Results
- Not posted in the source record
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, multicenter, single-arm study to assess the safety and feasibility of combining crenolanib with fludarabine and cytarabine chemotherapy in pediatric patients with relapsed/refractory FLT3-mutated AML. Patients will receive up to two courses of salvage chemotherapy with fludarabine, cytarabine, and crenolanib. Response will be assessed between day 29-43 of each course.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Crenolanib | Experimental | Drug: Crenolanib, Drug: Fludarabine, Drug: Cytarabine |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Age ≥ 1 years and ≤ 21 years
- Confirmed diagnosis of AML according to World Health Organization (WHO) 2016 classification
- Definitive evidence of a FLT3-ITD and/or FLT3-TKD (D835/I836) mutation at the time of enrollment
- Patients must have histologically or molecularly confirmed relapsed or refractory AML
- Karnofsky or Lansky performance score ≥ 50. Use Karnofsky for patients > 16 years old and Lansky for patients ≤ 16 years of age.
Key exclusion criteria (17 listed)
- Patients with any of the following current or previous diagnoses:
- Patients who are refractory to first line (induction and re-induction) and a second line (1st salvage) treatment for AML.
- Patients who have received more than 1 prior allogeneic HSCT
- Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection of which they exhibit ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
- Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
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: Crenolanib besylate66.7 mg/m2 three times a day (TID) | Drug | Crenolanib |
| Fludarabine30 mg/m2/day, intravenous infusions over 30 mins. | Drug | Crenolanib |
| Cytarabine2000 mg/m2/day, intravenous infusions over 1-3 hours. | Drug | Crenolanib |
Primary outcome
Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0
Time frame: From study entry to 30 days post-treatment
Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0
Time frame: 60 days
Rate of early mortality
Time frame: 60 days
Number of patients who died within 60 days of start of therapy
3 secondary outcomes
Event-free survival (EFS)
Time frame: 4 years
Relapse-free survival (RFS)
Time frame: 4 years
Overall survival (OS)
Time frame: 4 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Crenolanib, Fludarabine and Cytarabine in people with Relapsed/Refractory FLT3-mutated AML, run by Arog Pharmaceuticals, Inc..
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 12 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: withdrawn, as of the sponsor's last update on 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0 (time frame: From study entry to 30 days post-treatment). The study lists 3 primary outcomes in all. 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 10 Jan 2019.