Phase 1/2 Safety and Efficacy of PLX3397 in Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML)
This trial is active, not recruiting.
|Condition||acute myeloid leukemia|
|Phase||phase 1/phase 2|
|Start date||November 2011|
|End date||December 2017|
|Trial size||90 participants|
|Trial identifier||NCT01349049, PLX108-05|
The purpose of this study is to evaluate the safety of study drug PLX3397 at 3 dose levels (800 mg/day, 1000 mg/day, and 1200 mg/day) and explore the efficacy in patients with relapsed or refractory acute myeloid leukemia (AML). Additional dose levels beyond 1200 mg/day may be considered based on safety and efficacy observations.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|San Francisco, CA||UCSF Medical Center-Mount Zion||no longer recruiting|
|San Francisco, CA||UCSF Helen Diller Family Family Comprehensive Cancer Center||no longer recruiting|
|Chicago, IL||Northwestern University||no longer recruiting|
|Baltimore, MD||Johns Hopkins University||no longer recruiting|
|Baltimore, MD||Johns Hopkins University / Sidney Kimmel Cancer Center||no longer recruiting|
|Boston, MA||Brigham and Women's Hospital||no longer recruiting|
|Boston, MA||Dana Farber Cancer Institute||no longer recruiting|
|Buffalo, NY||Roswell Park Cancer Institute||no longer recruiting|
|New York, NY||Memorial Sloan Kettering Cancer Center||no longer recruiting|
|New York, NY||Memorial Sloan-Kettering Cancer Center||withdrawn|
|Philadelphia, PA||University of Pennsylvania, Abramson Cancer Center||no longer recruiting|
|Seattle, WA||Fred Hutch / University of Washington Cancer Consortium||no longer recruiting|
|Intervention model||single group assignment|
Safety-Subject incidence of adverse events
time frame: 1 year
Complete Remission (CR) Rate including complete remission with incomplete blood count recovery (CRi)
time frame: 1 year
All participants at least 18 years old.
- Male or female patients ≥18 years old.
- Morphologically documented primary AML, prior-chemotherapy-related AML or AML secondary to an antecedent hematologic disorder (e.g., Myelodysplastic Syndrome) as defined by WHO criteria, confirmed by pathology review. For Cohort Expansion Phase (Part 2) only: Bone marrow involvement is required.
- Have either relapsed or refractory AML, or who have newly diagnosed Flt3-ITD positive AML but either refuse or are considered by the Investigator not to be an appropriate candidate for standard chemotherapy.
- Relapsed disease is defined as the reappearance of leukemia cells in the bone marrow or peripheral blood or elsewhere in the body (other tissues/organs) after the attainment of a CR.
- Refractory disease is defined by the failure to obtain a complete remission (CR) with a HDAC-containing or a standard induction regimen. Patients who require two cycles of induction therapy to attain a first CR are not considered to have refractory disease.
- Positive for Flt3-ITD activating mutations during Screening. Local laboratory results must be received prior to enrollment. Patients with a history of Flt3-ITD positive disease may be considered after discussion with the Medical Monitor.
- ECOG performance status of 0, 1, or 2.
- Adequate recovery (to at least Grade 1) from toxicity of prior therapy as follows:
- ≥2 weeks for cytotoxic therapy (except hydroxyurea, which is permitted at doses of ≤5g/day during the first 2 weeks of Cycle 1) prior to C1D1.
- ≥4 half-lives for non-cytotoxic therapy prior to C1D1. Patients must have a wash-out period from their last chemotherapy of either ≥2 weeks OR at least 4 half-lives prior to C1D1. For patients whose most recent anti-tumor treatment regimen consisted of a multi-agent cocktail, the patient must have a wash-out period of at least 4 half-lives of the agent with the longest half-life.
- Adequate hepatic and renal function
- Adequate renal function, defined as Creatinine Clearance >60 mL/min or serum creatinine of ≤ 1.3 mg/dL (115 μM).
- Adequate hepatic function, defined as AST and ALT ≤3.0X ULN and serum direct bilirubin ≤1.5X ULN. Exceptions may be made for patients with elevated liver transaminases secondary to AML after discussion with the Medical Monitor
- Life expectancy of at least 1 month
- Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements and for 3 months after last dose.
- Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use two acceptable methods of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they meet at least one of the following criteria:
- Surgically sterile
- Have been postmenopausal for ≥1 year
- Have FSH levels indicative of postmenopausal state (i.e., 30-120 IU/L) documented within 21 days of C1D1. Sexually active men must also agree to use an acceptable method of birth control while on study drug and for at least 3 months after the last dose
- Diagnosis of acute promyelocytic leukemia
- Diagnosis of chronic myelogenous leukemia in blast crisis
- Presence of CNS involvement of leukemia. Patients with a history of CNS involvement may be considered after discussion with the Medical Monitor
- Patients eligible for HSCT at the time of screening. However, patients who meet one or both of the following criteria may be eligible for study participation:
- Patients who are eligible for HSCT but with non-optimal AML disease control (i.e., blasts > 5%) may be enrolled into this study as a bridge-to-transplant.
- Patients with relapsed disease following a prior HSCT may be enrolled into this study as an alternative to a second HSCT or as a bridge-to-transplant regimen.
- For both Parts 1 and 2, receipt of HSCT within 60 days of the first dose of PLX3397 is an exclusion criterion. Patients on immunosuppressive therapy post HSCT, or with clinically significant graft-versus-host disease are excluded from Part 1. (Use of topical steroids for ongoing skin GVHD is permitted). Patients for Part 1 must have a wash-out period of ≥2 weeks or at least 4 half-lives from their last systemic immunosuppressive treatment for GVHD. Patients for Part 2 may be receiving systemic immunosuppressive treatment for management of GVHD at the time of screening and enrollment
- Investigational drug use within 28 days of the first dose of PLX3397
- For Cohort Expansion Phase (Part 2) only: Patients who are positive for the D835 mutation at Screening are excluded.
- A concurrent active cancer that requires non-surgical therapy (e.g., chemotherapy, radiation, adjuvant therapy). Prior history of other cancer is allowed, as long as there is no active disease within 1 year of the first dose of PLX3397.
- Refractory nausea and vomiting, malabsorption, biliary shunt significant bowel resection, GVHD affecting the gut, or any other condition that would preclude adequate absorption
- Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
- Women of child-bearing potential who are pregnant or breast feeding
- At Screening, QTcF >450 msec for males; QTcF >470 msec for females
- Patients with a history of D835 mutations
|Official title||A Phase 1/2 Safety and Efficacy Study of Orally Administered PLX3397 in Adults With Relapsed or Refractory FLT3-ITD Positive Acute Myeloid Leukemia (AML)|
|Principal investigator||Olga Frankfurt, MD|
|Description||Protocol PLX108-05 is a Phase 1/2 open-label, sequential dose escalation (Part 1) followed by cohort expansion (Part 2) design at the recommended phase 2 dose established in Part 1 (i.e. 3,000 mg/day). Treatment with PLX3397 will consist of continuous oral administration in 28-day cycles until unacceptable or dose-limiting toxicity, disease progression or relapse, patient death, Investigator decision, or voluntary withdrawal.|
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