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A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Patients With Relapsed or Refractory Acute Myeloid Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02545283
First received: August 31, 2015
Last updated: March 10, 2017
Last verified: March 2017
  Purpose
This study is designed to compare Overall Survival (OS) in participants with relapsed or refractory Acute Myeloid Leukemia (AML) treated with idasanutlin in combination with cytarabine versus participants treated with placebo and cytarabine. Participants will receive induction treatment with idasanutlin/placebo and cytarabine (Cycle 1). Responding patients may continue to receive a maximum of further two cycles of consolidation (Cycle 2 and Cycle 3). Complete remission (CR), CR with incomplete platelet count recovery (CRp), overall remission rate (ORR), event-free survival (EFS), leukemia-free survival (LFS) and percentage of participants with an allogeneic hematopoietic stem cell transplant (HSCT) will also be compared between treatment arms. This study will include participants without (TP53 wild-type) and with TP53 mutations.

Condition Intervention Phase
Neoplasms, Leukemia, Acute Myeloid Leukemia
Drug: Cytarabine
Drug: Idasanutlin
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase III Study of Idasanutlin, an MDM2 Antagonist, With Cytarabine Versus Cytarabine Plus Placebo in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Overall Survival (OS) in TP53 Wild-Type Population [ Time Frame: From start of study up to 4.5 years ]

Secondary Outcome Measures:
  • Overall Survival (OS) in the Overall Population [ Time Frame: From start of study up to 4.5 years ]
  • Percentage of Participants in Complete Remission with incomplete blood count recovery (CRi) [ Time Frame: From start of study up to 4.5 years ]
  • Overall Remission Rate (ORR), including CR, CRp and CRi [ Time Frame: From start of study up to 4.5 years ]
  • Event Free Survival (EFS) [ Time Frame: From start of study up to 4.5 years ]
  • Leukemia Free Survival (LFS) [ Time Frame: From start of study up to 4.5 years ]
  • Apparent Clearance (CL/F) of Idasanutlin [ Time Frame: Cycle 1 (28 Days) Days 1, 2, 5, 8 and 10 and Cycles 2 and 3 (28 Days) Days 2 and 5 ]
  • Apparent Volume of Distribution (Vd/F) of Idasanutlin [ Time Frame: Cycle 1 (28 Days) Days 1, 2, 5, 8 and 10 and Cycles 2 and 3 (28 Days) Days 2 and 5 ]
  • Maximum Concentration Observed (Cmax) of Idasanutlin [ Time Frame: Cycle 1 (28 Days) Days 1, 2, 5, 8 and 10 and Cycles 2 and 3 (28 Days) Days 2 and 5 ]
  • Steady-State Concentration (C trough) of Idasanutlin [ Time Frame: Cycle 1 (28 Days) Days 1, 2, 5, 8 and 10 and Cycles 2 and 3 (28 Days) Days 2 and 5 ]
  • Area Under the Concentration-Time Curve (AUC) of Idasanutlin [ Time Frame: Cycle 1 (28 Days) Days 1, 2, 5, 8 and 10 and Cycles 2 and 3 (28 Days) Days 2 and 5 ]
  • Half-Life (t 1/2) of Idasanutlin [ Time Frame: Cycle 1 (28 Days) Days 1, 2, 5, 8 and 10 and Cycles 2 and 3 (28 Days) Days 2 and 5 ]
  • Total clearance (CL) of Cytarabine [ Time Frame: Cycle 1 (28 Days) Days 1, 2 and 5 and Cycles 2 and 3 (28 Days) Day 2 ]
  • Volume of Distribution (Vd) of Cytarabine [ Time Frame: Cycle 1 (28 Days) Days 1, 2 and 5 and Cycles 2 and 3 (28 Days) Day 2 ]
  • Percentage of Participants with Hematopoietic Stem Cell Transplant (HSCT) Following Response [ Time Frame: From start of study up to 4.5 years ]
  • Percentage of Participants with Adverse Events [ Time Frame: From start of study up to 4.5 years ]
  • Percentage of Participants in Complete Remission with Incomplete Platelet Count Recovery (CRp) [ Time Frame: From start of study up to 4.5 years ]
  • Percentage of Participants in Complete Remission (CR) [ Time Frame: From start of study up to 4.5 years ]
  • Percentage of Participants With Clinically Significant Changes in Safety Measurements [ Time Frame: From start of study up to 4.5 years ]
  • Score in Patient-Reported Outcome (PRO) Measures [ Time Frame: From start of study up to 4.5 years ]

Estimated Enrollment: 440
Actual Study Start Date: December 30, 2015
Estimated Study Completion Date: June 5, 2019
Estimated Primary Completion Date: June 5, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Idasanutlin plus Cytarabine
Participants are treated with idasanutlin orally twice daily and intravenous cytarabine once daily for 5 days followed by 23 days of rest (Cycle 1). Responding patients may continue to receive a maximum of further two cycles of consolidation (Cycle 2 and Cycle 3).
Drug: Cytarabine
1 g/m^2 cytarabine administered once daily as an intravenous infusion
Drug: Idasanutlin
300 mg idasanutlin administered orally twice daily
Placebo Comparator: Placebo plus Cytarabine
Participants are treated with placebo orally twice daily and intravenous cytarabine once daily for 5 days followed by 23 days of rest. Responding patients may continue to receive a maximum of further two cycles of consolidation (Cycle 2 and Cycle 3).
Drug: Cytarabine
1 g/m^2 cytarabine administered once daily as an intravenous infusion
Other: Placebo
Placebo administered orally twice daily

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >=18 years
  • Documented/confirmed 1st/2nd refractory/relapsed acute myeloid leukemia (AML) using World Health Organization classification, except acute promyelocytic leukemia.
  • No more than 2 prior induction regimens (excluding prior hematopoietic stem cell transplant [HSCT]) and one must have included cytarabine with an anthracycline (or anthracenedione)
  • Eastern Cooperative Oncology Group performance status of 0 to 1
  • Patient should be a potential candidate for allogeneic HSCT
  • Adequate hepatic and renal function

Exclusion Criteria:

  • Patients with first complete remission (CR1) duration of >1 year AND age <60 years
  • Patients with AML with myelodysplasia related changes, or AML that has developed as a consequence of an antecedent hematological disorder (AHD)
  • AML secondary to any prior chemotherapy unrelated to leukemia
  • Patients who have received more than two prior cytarabine containing induction regimens for AML
  • Patients who have relapsed within 90 days after therapy with intermediate-dose cytosine arabinoside (IDAC) or high-dose cytosine arabinoside (HiDAC) containing regimens
  • Patients who have received allogeneic HSCT within 90 days prior to randomization.
  • Patients who have received immunosuppressive therapy for graft versus host disease (G versus HD) within 2 weeks prior to study start
  • Prior treatment with a Murine Double Minute 2 (MDM2) antagonist
  • Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy
  • Patients with a history of other malignancy within 5 years prior to screening.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Pregnant or breastfeeding patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02545283

Contacts
Contact: Reference Study ID Number: WO29519 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@roche.com

  Show 82 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02545283     History of Changes
Other Study ID Numbers: WO29519
2014-003065-15 ( EudraCT Number )
Study First Received: August 31, 2015
Last Updated: March 10, 2017

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 24, 2017