Phase 1/2 Safety and Efficacy of PLX3397 in Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML)

This study is currently recruiting participants.
Verified September 2013 by Plexxikon
Sponsor:
Information provided by (Responsible Party):
Plexxikon
ClinicalTrials.gov Identifier:
NCT01349049
First received: May 4, 2011
Last updated: September 7, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: PLX3397
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Safety and Efficacy Study of Orally Administered PLX3397 in Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Plexxikon:

Primary Outcome Measures:
  • Safety-Subject incidence of adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Subjects will take oral doses of PLX3397 twice a day. Physical examinations, vital signs, 12-lead electrocardiograms (ECG), adverse events, hematology and serum chemistry will be used to assess safety throughout the study. Adverse events will be monitored and reviewed for safety issues/abnormal changes in the above mentioned tests.

  • Complete Remission (CR) Rate including complete remission with incomplete blood count recovery (CRi) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Evaluated by bone marrow assessments at a minimum of once every month. Evaluated using the International Working Group Response Criteria (Cheson 2003).


Estimated Enrollment: 45
Study Start Date: November 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PLX3397
Subjects will be dosed at the maximum tolerated dose.
Drug: PLX3397
Maximum Tolerated Dose of PLX3397 will be administered orally, twice daily.
Experimental: oral dose of 800 mg/day of PLX3397 Drug: PLX3397
The drug product is available in capsule form, to be taken orally.
Experimental: oral dose of 1000 mg/day PLX3397 Drug: PLX3397
The drug product is available in capsule form, to be taken orally.
Experimental: oral dose of 1200 mg/day PLX3397 Drug: PLX3397
The drug product is available in capsule form, to be taken orally.
Experimental: oral dose of 1400 mg/day PLX3397 Drug: PLX3397
The drug product is available in capsule form, to be taken orally.
Experimental: oral dose of 2000 mg/day PLX3397 Drug: PLX3397
The drug product is available in capsule form, to be taken orally.
Experimental: oral dose of 3000 mg/day PLX3397 Drug: PLX3397
The drug product is available in capsule form, to be taken orally.
Experimental: oral dose of 4000 mg/day PLX3397 Drug: PLX3397
The drug product is available in capsule form, to be taken orally.
Experimental: oral dose of 5000 mg/day PLX3397 Drug: PLX3397
The drug product is available in capsule form, to be taken orally.

Detailed 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, elective allogeneic hematopoietic stem cell transplantation, disease progression or relapse, patient death, Investigator decision, or voluntary withdrawal.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients ≥18 years old
  • Morphologically documented primary Acute Myeloid Leukemia (AML), prior chemotherapy-related AML, or AML secondary to an antecedent hematologic disorder (e.g. MDS), as defined by World Health Organization (WHO) criteria, confirmed by pathology review at the treating institution. Bone marrow involvement is required for Cohort Expansion Phase (Part 2)only.
  • In at least first relapse or refractory AML; patients ≥ 60 years old can be included if unable or unwilling to undergo induction chemotherapy for hematopoietic stem cell transplantation (HSCT)
  • Positive for Flt3-ITD activating mutation during Screening
  • ECOG performance status of 0, 1, or 2
  • Adequate recovery (to at least Grade 1) from toxicity of prior therapy as follows:

    • ≥2 weeks prior to C1D1 for cytotoxic therapy (excluding hydroxyurea, which is permitted at doses less than or equal to 5 g/day during first 2 weeks of cycle 1)
    • ≥4 half-lives for non-cytotoxic therapy prior to C1D1; washout period from last chemotherapy of at least 2 weeks OR at least 4 half-lives prior to C1D1.

      • Adequate renal and hepatic function
    • Adequate renal function, defined as Creatinine Clearance > 60 ml/min. or serum creatinine <=1.3 mg/dl (115 uM).
    • 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.
  • 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
  • Women of child-bearing potential must have a negative serum 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 follicle stimulation hormone (FSH) levels indicative of postmenopausal state (i.e. 30-120 IU/L) Sexually active men must also agree to use an acceptable method of birth control while on study drug and for 3 months after last dose.

Exclusion Criteria:

  • Diagnosis of acute promyelocytic leukemia
  • Diagnosis of chronic myelogenous leukemia in blast crisis
  • Presence of CNS involvement of leukemia [discuss with Medical Monitor]
  • Eligible for hematopoietic stell cell transplant (HSCT) at time of screening. However, patients who meet both of the following criteria may be eligible for study participation:

    1. eligible for HSCT but with non-optimal AML disease control (i.e., blasts greater than 5 percent) may be enrolled as bridge-to-transplant.
    2. relapsed disease following prior HSCT may be enrolled as alternative to second HSCT or as bridge-to-transplant regimen.
  • Receipt of HSCT within 60 days of the first dose of PLX3397, on immunosuppressive therapy post HSCT at the time of Screening, or with clinically significant graft-versus-host disease. [Use of topical steroids for ongoing skin (Graft versus Host Disease) (GVHD) is permitted)
  • Investigational drug use within 28 days of the first dose of PLX3397
  • Disease positive for D835 mutation at Screening; history of D835 mutations.
  • 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 was no active disease within 1 year.
  • 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
  • QTcF ≥ 450 msec for males; QTcF ≥ 470 msec for females.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01349049

Contacts
Contact: Mai Le, MD mle@plexxikon.com
Contact: Henry Hsu, MD hhsu@plexxikon.com

Locations
United States, California
UCSF Helen Diller Family Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143
Contact: Adrienne Moran       morana@cc.ucsf.edu   
Principal Investigator: Catherine Smith, MD         
Sub-Investigator: Neil Shah, MD, PhD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Kristina Nickel       k-nickel@northwestern.edu   
Principal Investigator: Olga Frankfurt, MD         
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21231
Contact: Emily Palmisano Lederer, RN, MS       epalmis1@jhmi.edu   
Principal Investigator: Mark Levis, MD, PhD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Caitlin Driscoll       cddriscoll@partners.org   
Principal Investigator: Richard Stone, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Wendy Walinski       wendy.walinski@roswellpark.org   
Principal Investigator: Eunice Wang, MD         
New York Presby Hospital, Weill Medical College at Cornell University Recruiting
New York, New York, United States, 10065
Contact: Yulia Dault, RN       yud9001@med.cornell.edu   
Principal Investigator: Gail Roboz, MD         
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10022
Contact: Jeff Martinez       martinj8@mskcc.org   
Principal Investigator: Etyan Stein, MD         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kim Hummel       kim.hummel@uphs.upenn.edu   
Principal Investigator: Alexander Perl, MD         
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Lori Jarrett       ljarrett@fhcrc.org   
Principal Investigator: John Pagel, MD, PhD         
Sponsors and Collaborators
Plexxikon
  More Information

No publications provided

Responsible Party: Plexxikon
ClinicalTrials.gov Identifier: NCT01349049     History of Changes
Other Study ID Numbers: PLX108-05
Study First Received: May 4, 2011
Last Updated: September 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Plexxikon:
AML
relapsed
refractory

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on April 15, 2014