TerminatedPhase 3

Study of Crenolanib in Combination With Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Activating FLT3 Mutations

Stopped: The manufacturer Arog Pharmaceuticals Inc has terminated the Agreement Concerning the Support of an Investigator Initiated Trial this became valid on 2020/03/09

Germany9 participantsStarted 2016-11-17

Plain-language summary

The main trial is a double-blinded, placebo-controlled, randomized, phase III, multi-center trial in adult patients with relapsed or refractory AML harboring an activating FLT3 mutation as defined in the inclusion /exclusion criteria. An initial open label dose-finding run-in phase I of the study will be performed administering the study drug crenolanib with salvage chemotherapy consisting of mitoxantrone and cytarabine (MC) in 18 patients according to the experimental arm of the study. After completion of this dose-finding run-in phase I, toxicity and response data will be provided to the external Data and Safety Monitoring Board (DSMB) and the Trial Committee by the Coordinating Investigator. The Trial Committee will decide on the basis of these data and the recommendation of the DSMB on dose modification and the further conduct of the study with regard to the double-blinded, placebo-controlled, randomized phase of the study. The double-blinded, placebo-controlled randomized portion will start after the completion of the dose-finding run-in phase I and positive opinion of the Trial Committee. Crenolanib starts on day 7 of MC and is given continuously until 48 hours prior to the next chemotherapy; if receiving allogeneic HCT, crenolanib is held 48 hours prior to conditioning and restarts no sooner than 30 days and not later than day 100 after transplant. Sample size randomized phase: 276 patients Primary objective: To evaluate the impact of crenolanib given in combination with salvage chemotherapy and consolidation including allogeneic hematopoietic cell transplantation and ongoing single agent maintenance therapy with crenolanib on event-free (EFS) and overall survival (OS) in adult patients with relapsed or refractory AML harboring FLT3 activating mutations.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Patients with confirmed diagnosis of AML either refractory to induction therapy or relapsed after first line treatment including chemotherapy, autologous and allogeneic HCT
✓. refractory to induction therapy is defined as no CR, CRi, PR (according to standard criteria, 28) after one intensive induction therapy including at least 7 days of cytarabine 100-200mg/m² continuously or an equivalent regimen with cytarabine with total dose not less than 700mg/m² per cycle and 3 days of an anthracycline (e.g. daunorubicin, idarubicin)
✓. relapsed after first line therapy is defined as relapsed AML (according to standard criteria, 28) after a first line therapy including at least one intensive induction and consolidation therapy
✓. Presence of FLT3-activating mutation at the time of refractory disease or relapse assessed in the central AMLSG reference laboratory within AMLSG BiO study (ClinicalTrials.gov Identifier: NCT01252485); positivity of FLT3-ITD and FLT3-TKD is defined based on genescan analysis with a mutant to wild-type ratio equal or above 5%
✓. Patients considered eligible for intensive chemotherapy
✓. ECOG performance status of ≤ 2
✓. Age ≥ 18 years with the capacity to give written informed consent
✓. Non-pregnant and non-nursing women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).

What they're measuring

Event-free Survival (EFS)

Timeframe: 4 years

Overall Survival (OS)

Timeframe: 4 years

Trial details

NCT IDNCT02298166

SponsorUniversity of Ulm

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2020-03-09

View on ClinicalTrials.gov More Acute Myeloid Leukemia trials

Plain-language summary

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Patients with confirmed diagnosis of AML either refractory to induction therapy or relapsed after first line treatment including chemotherapy, autologous and allogeneic HCT
✓. refractory to induction therapy is defined as no CR, CRi, PR (according to standard criteria, 28) after one intensive induction therapy including at least 7 days of cytarabine 100-200mg/m² continuously or an equivalent regimen with cytarabine with total dose not less than 700mg/m² per cycle and 3 days of an anthracycline (e.g. daunorubicin, idarubicin)
✓. relapsed after first line therapy is defined as relapsed AML (according to standard criteria, 28) after a first line therapy including at least one intensive induction and consolidation therapy
✓. Presence of FLT3-activating mutation at the time of refractory disease or relapse assessed in the central AMLSG reference laboratory within AMLSG BiO study (ClinicalTrials.gov Identifier: NCT01252485); positivity of FLT3-ITD and FLT3-TKD is defined based on genescan analysis with a mutant to wild-type ratio equal or above 5%
✓. Patients considered eligible for intensive chemotherapy
✓. ECOG performance status of ≤ 2
✓. Age ≥ 18 years with the capacity to give written informed consent
✓. Non-pregnant and non-nursing women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).

Study of Crenolanib in Combination With Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Activating FLT3 Mutations

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Study of Crenolanib in Combination With Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Activating FLT3 Mutations

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Exclusion criteria