Clinical Trials

Acute Myeloid Leukemia (AML)

  • ARO-004

    Phase II Study of Crenolanib in Subjects With Relapsed/Refractory AML With FLT3 Activating Mutation (NCT01522469)

    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.

    For more information please see: clinicaltrials.gov

  • ARO-005

    A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations (NCT01657682)

    This is a Phase II open-label study of crenolanib besylate. This study will enroll subjects with relapsed acute myeloid leukemia (AML) with FLT3 activating mutations. Two cohorts of patients will be enrolled: those whose AML has recurred after prior chemotherapy (not including a FLT3 TKI), and those whose AML has progressed after prior therapy with a FLT3 TKI. Subjects will take crenolanib in three doses daily until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Concurrent hydroxyurea is permitted during the first 28 days of study therapy.

    For more information please see: clinicaltrials.gov

  • ARO-006

    A Safety and Tolerability Study of Crenolanib in Combination With Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia Patients With FLT3 Mutations (NCT02283177)

    This is a double arm, Phase II study in newly diagnosed FLT-3 positive Acute Myeloid Leukemia (AML) patients scheduled to start at the University of Texas: Southwestern in the first quarter of 2015. Patients with FLT3-D835 mutations, FLT3-ITD (internal tandem duplications), or compound mutations will be eligible and receive daily doses of 100 mg crenolanib TID in combination with Ara-C + daunorubicin or Ara-C + idarubicin.

    For more information please see: clinicaltrials.gov

  • ARO-007

    Study of Crenolanib in Combination With Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Activating FLT3 Mutations (NCT02298166)

    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 safety run-in phase of the study will be performed in an open-label setting administering the study drug crenolanib with salvage chemotherapy consisting of mitoxantrone and cytarabine (MC) in 12 patients according to the experimental arm of the study. After completion of this safety run-in phase, 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 safety run-in phase and positive opinion of the Trial Committee.

    For more information please see: clinicaltrials.gov

  • ARO-008

    Crenolanib in Combination with Sorafenib in Patients with Refractory or Relapsed Hematologic Malignancies (NCT02270788)

    This is a pilot study to characterize the toxicity profile, to determine the maximum tolerated dose of the combination of crenolanib and sorafenib, and to determine the feasibility of administering these drugs in patients under the age of 25 with relapsed or refractory hematologic malignancies, including acute myeloid leukemia (AML), AML with prior myelodysplastic syndrome (MDS), and myeloperoxidase (MPO)-positive mixed phenotype acute leukemia with FLT3-internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations.

    The study will include two phases:

    • The dose-escalation phase will characterize the dose-limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD) or recommended Phase II dose (RP2D) of crenolanib when given in combination with sorafenib.
    • The dose-expansion cohort will further assess the safety and explore the efficacy of this combination.

     

    For more information please see: clinicaltrials.gov

  • ARO-009

    A Safety and Tolerability Study of Crenolanib Maintenance Following Allogeneic Stem Cell Transplantation in Patients with FLT3 positive Acute Myelogenous Leukemia

    This is a Phase II study of crenolanib given as a single agent post-allogeneic transplant to patients diagnosed with FLT3 mutant acute myelogenous leukemia (AML) to assess safety and tolerability. Patients will be separated into either haploidentical or non-haploidentical post-transplant cohorts and will be treated with 100 mg crenolanib TID for up to one year barring progression or unacceptable toxicity.

  • ARO-010

    Multi-agent Phase I/II Study of Crenolanib in Relapsed/Refractory AML patients

    This is a Phase I/II study of crenolanib combined with idarubicin and cytarabine, and crenolanib combined with 5-azacitadine in Acute Myeloid Leukemia (AML) patients with FLT3 activating mutations scheduled to open the first quarter of 2015 at the MD Anderson Cancer Center. Patients will either be given 100 mg Crenolanib TID in combination with HiDAC or 5-Azacitadine to determine DLT, MTD, and response rate of these combination therapies. Following remission, patients will continue on crenolanib for up to a year.

 

Gastrointestinal Stromal Tumor (GIST)

  • ARO-002

    Phase II Study of Crenolanib (CP-868,596), for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions in the PDGFRA Gene (NCT01243346)

    This Phase II study is designed to evaluate the antitumor efficacy and pharmacokinetics of crenolanib in patients with D842-related mutant metastatic GIST. Twenty patients were treated under this trial at Fox Chase Cancer Center and Oregon Health and Science University.

    For more information please see: clinicaltrials.gov


    A patient showed a marked reduction in glucose uptake after 20 days of crenolanib exposure1
     

  • ARO-012

    Phase III Monotherapy of Crenolanib in Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations

    This is a Phase III study of crenolanib in patients with advanced PDGFRA-D842 related gastrointestinal stromal tumors (GIST) opening in multiple centers in Europe.

 

Glioma

  • ARO-001

    A Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas (NCT01229644)

    The purpose of this study is to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma.

    For more information please see: clinicaltrials.gov

  • ARO-003

    PDGFR Inhibitor Crenolanib in Children/Young Adults With Diffuse Intrinsic Pontine Glioma or Recurrent High-Grade Glioma (NCT01393912)

    This is a Phase I clinical trial evaluating crenolanib (CP-868,596), an inhibitor of Platelet Derived Growth Factor Receptor (PDGFR)-kinase in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum A) or in recurrent, progressive or refractory High Grade Glioma (HGG) including DIPG (Stratum B). This study drug targets the most commonly amplified region of the genome found in DIPG and pediatric high grade glioma (HGG) which encodes for the PDGF receptor kinase. An oral investigational agent crenolanib will be administered daily during and after local radiation therapy (RT) in Diffuse Intrinsic Pontine Glioma DIPG (Stratum A), or daily for children with recurrent/refractory HGG (Stratum B).

    For more information please see: clinicaltrials.gov

 

1Matro et al., ASCO 2014