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).
- Conditions
- leukemiaRelapsed or Refractory acute myeloid leukemia10024324
- Registration Number
- NL-OMON47508
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
- Age * 18 years,
- Documented/confirmed 1st/2nd refractory/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 (excl. 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 * 2
- Adequate hepatic function assessed by the following: Serum total bilirubin *
1.5 x institutional upper limit of normal (ULN), unless resulting from
hemolysis, Gilbert*s syndrome, or liver infiltration with leukemia. AST/ALT * 3
x institutional ULN (or * 5 x upper limit of institutional laboratory reference
range if liver infiltration with leukemia)
- Adequate renal function assessed by serum creatinine within reference
laboratory ranges OR creatinine clearance (by Cockcroft Gault formula) * 50
mL/min.,
- WBC count at randomization of *50.000/mm3
Note: When treatment is not started immediately upon randomization, the WBC
count at the start of induction therapy (C1) must remain at *50.000/mm3. The
use of hydroxyurea (HU) or leukapheresis to meet eligibility is allowed. HU or
leukapheresis must be discontinued at least 24 hours prior to the initiation of
study medication.
- For women of childbearing potential: agreement to remain abstinent (refrain
from heterosexual intercourse) or use two adequate methods of contraception,
including at least one method with a failure rate of < 1% per year, during the
treatment period and for up to 6 months after the last dose of study drug.
Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, and established, proper use of
hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine
devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception. Barrier methods must always be supplemented with the use of a
spermicide., - For men unless permanently sterile by bilateral orchidectomy:
agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm, as defined
below:
With female partners of childbearing potential or pregnant female partners, men
must remain abstinent or use a condom during the treatment period and for up to
6 months after the last dose of study drug. Men must refrain from donating
sperm during this same period.
The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient., - Ability to understand and willingness to sign a written informed
consent form and comply with all study requirements including completion of PRO
measures.
- First relapsed patients with CR1 duration of >1 year AND age <60 years,
- Patients with prior documented AHD including the following: myelodysplastic
syndrome, myeloproliferative disease (i.e., chronic myelomonocytic leukemia,
polycythemia vera, primary myelofibrosis, and essential thrombocythemia), and
aplastic anemia,
- AML secondary to any prior chemotherapy unrelated to leukemia,
- Patients who are either refractory to or have relapsed within 90 days of
receiving a regimen containing a cumulative dose of * 18 g/m2 cytarabine,
- Patients who have received allogeneic HSCT within 90 days prior to
randomization. HSCT should have been performed in remission and not used for
salvage (patients who have received autologous HSCT as consolidation in CR1 are
eligible).,
- Patients who have received immunosuppressive therapy for graft versus host
disease (GvHD) 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 (or 5 half-lives) from first receipt of study drug. Note: The exception is
HU or leukapheresis in patients who need to continue this therapy to maintain a
WBC count * 50,000/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 which
have not resolved to Grade * 2 per National Cancer Institute Common Terminology
Criteria for Adverse Events (NCI 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
as defined inTable 3, Table 4, and Table 5 of the protocol 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 (see protocol).
- Patients with history of systemic hypersensitivity reactions * grade 2
attributed to cytarabine or components of the formulated product,
- Patients who have any severe and/or uncontrolled medical conditions or other
conditio
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method