A Study of Idasanutlin with Cytarabine versus Cytarabine plus Placebo in Patients with Relapsed or Refractory Acute Myeloid Leukemia.
- Conditions
- Relapsed or refractory acute myeloid leukemia (AML).MedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003065-15-GB
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 440
- Age >=18 years
- Documented/confirmed first or second refractory or relapsed AML using World Health Organization classification, except acute promyelocytic leukemia and first relapsed AML patients with a CR1 duration of >1 year AND age < 60 years
- No more than 2 prior induction regimens (excluding prior HSCT) in their first line treatment and one must have included cytarabine with an anthracycline (or anthracenedione)
- Eastern Cooperative Oncology Group performance status of 0 to 2
- Adequate hepatic and renal function
- WBC count at randomization of <=50,000/ cubic millimeter (mm3).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 176
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 264
- First relapsed patients aged < 60 years with a CR1 duration of > 1 year
- Patients with prior documented antecedent hematological disorder (AHD)
- AML secondary to any prior chemotherapy unrelated to leukemia
- Patients who are either refractory to/or relapsed within 90 days of receiving a regimen containing a cumulative dose of >=18 gram/square meter cytarabine
- Patients who have received allogeneic HSCT within 90 days prior to randomization
- Patients who have received immunosuppressive therapy for graft-versus-host disease or for engraftment syndrome after autologous stem cell transplantation within 2 weeks prior to randomization
- Prior treatment with a Murine Double Minute 2 (MDM2) antagonist
- Patients with clinically relevant QTc prolongation (QTcF > 480 ms), a family history of long QT syndrome, or who are currently receiving treatment with medications that are known to prolong the QT interval
- Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 30 days from the first receipt of study drug with the exception of HU or leukapheresis in patients who need to continue this therapy to maintain a WBC count <=50000/mm3. HU or leukapheresis must be discontinued at least 24 hours prior to the initiation of study medication
- Patients with acute toxicities from any prior anti-leukemia therapy that have not resolved to Grade <=2 per National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE), Version 4.03
- Patients with a history of other malignancy within 5 years prior to screening except for malignancy that has been in remission without treatment for at least 2 years prior to randomization
- Patients unable to temporarily interrupt treatment with moderate to strong CYP2C8 inducers and inhibitors (including gemfibrozil, which is also an inhibitor of UGT1A3), CYP2C8 or OATP1B1/3 substrates, or strong CYP3A4 inducers during the treatment phase. These agents must be discontinued 7-14 days prior to the start of study medication
- Patients unable to temporarily interrupt treatment with oral or parenteral anticoagulants/anti-platelet agents (e.g., warfarin, chronic daily treatment with aspirin [> 325 mg/day], clopidogrel, dabigatran, apixaban, rivaroxaban) during the treatment phase. These agents must be discontinued 7 days (or 5 half-lives) prior to the start of study medication
Note: Treatment with or switch to low molecular weight heparin (LMWH) or unfractionated heparin (UFH) is allowed, according to local practice. However, platelet levels need to be closely monitored in these patients
- Patients with a history of systemic hypersensitivity reactions >=Grade 2 attributed to cytarabine
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could impair the ability of the investigator to evaluate the patient, or impair the patient’s ability to complete the study
- Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the patient upon the induction of neutropenia, that is, patients who are or should be on antimicrobial agents for the treatment of active infection
- Patients with extramedullary AML with no evidence of systemic involvement
- Pregnant or breastfeeding patients.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method