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A Study of Idasanutlin with Cytarabine versus Cytarabine plus Placebo in Patients with Relapsed or Refractory Acute Myeloid Leukemia.

Phase 1
Conditions
Relapsed or refractory acute myeloid leukemia (AML).
MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2014-003065-15-AT
Lead Sponsor
F. Hoffmann-La Roche Ltd
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Not specified
Target Recruitment
440
Inclusion Criteria

- 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

Exclusion Criteria

- 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 graftversus-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, or subcutaneous [SC] anticoagulant prophylaxis) 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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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