Primary Objective:To determine overall survival (OS) of Selinexor as compared to physician choice (PC) in patients * 60 years old with relapsed/refractory AML that requires treatment and are ineligible for intensive chemotherapy and/or…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary efficacy endpoint: Overall survival.
Secondary outcome
* The proportion of patients whose OS is at least 3 months (OS3.0)
* The complete remission rate (CRR), including complete remission with full
hematologic recovery (CR), and median disease free survival (DFS) for patients
who achieve CR
* The modified CRR (mCRR), including CR or CRi (including CRp), and median DFS
for patients who achieve CR or CRi (including CRp)
* The overall response rate (ORR) and duration of overall response (DOR),
including CR, CRi, MLFS, and partial remission (PR)
* The disease control rate (DCR) defined as ORR + stable disease for * 4 weeks
(SD), and duration of DCR
* Quality of life and patient reported outcomes (FACT-Leukemia and EQ-5D-5L)
(QoL)
The safety and tolerability of selinexor and PC will be evaluated by means of
drug-related AE reports, physical examinations, and laboratory safety
evaluations.
Background summary
Selinexor (oral) has shown single-agent, durable, anti-cancer activity in
patients with multiply relapsed or refractory hematologic and solid tumor
malignancies in initial Phase 1 dose escalation studies.
Selinexor show potent antiproliferative effect and induced apoptosis, cell
cycle arrest and myeloid differentiation in AML cell lines and patient blasts,
including those from patients with NPM1 and FLT3-ITD mutations (Ranganathan
2012).
Oral Selinexor may represent a novel treatment for AML in this
difficult-to-treat population.
Study objective
Primary Objective:
To determine overall survival (OS) of Selinexor as compared to physician choice
(PC) in patients * 60 years old with relapsed/refractory AML that requires
treatment and are ineligible for intensive chemotherapy and/or transplantation.
Secondary Objectives:
* To determine the proportion of patients whose OS is at least 3 months (OS3.0)
* To determine the complete remission rate (CRR), including complete remission
with full hematologic recovery (CR), and median disease free survival (DFS) for
patients who achieve CR
* To determine the modified CRR (mCRR), including CR or complete remission with
incomplete hematologic recovery (CRi) (including complete remission with
incomplete platelet recovery [CRp]), and median DFS for patients who achieve CR
or CRi (including CRp)
* To determine the overall response rate (ORR) and duration of overall response
(DOR), including CR, CRi, morphologic leukemia-free state (MLFS), and partial
remission (PR)
* To determine the disease control rate (DCR) defined as ORR + stable disease
for * 4 weeks (SD), and duration of DCR
* To assess the safety and tolerability of selinexor (KPT-330), as compared to
physician's choice (PC)
* Quality of life and patient reported outcomes (FACT-Leukemia, EQ-5D-5L) (QoL)
Study design
This is a randomized, multicenter, open-label, Phase 2 study of the SINE
Selinexor given orally versus specified investigator choices (one of three
potential salvage therapies). Approximately 300 patients will be enrolled,
with randomization of 2:1 Selinexor to PC arms.
One of the following three care regimens will be selected by the treating
physician investigator (physician's choice - PC):
(1) BSC including blood product transfusions, antimicrobials, growth factors as
needed, and hydroxyurea;
(2) BSC + low dose AraC, 20 mg bid by subcutaneous (sc) injection daily on Days
1-10/14 (20/28 doses) to be repeated at 28 to 42 day intervals; (3) BSC +
hypomethylating agent: azacitidine 75 mg/m2 by sc injection daily on Days 1-7
or 1-5 and 8-9 (7 doses) to be repeated at *28 day intervals, or decitabine (20
mg/m2 IV over 1 hour daily on days 1-5 or days 1-10 to be repeated at * 28 day
intervals).
Intervention
Study assessments:
sign informed consent, demographics, full ophthalmological and visual acuity
examination, 12-lead ECG, concomitant medication assessments, chest radiograph,
disease risk assessment according to ELN, physical examination, ECOG
performance status, BSA, Vital signs, urine dipstick, serum chemistry,
coagulation parameters, complete blood count, bone marrow aspirate (ore bipsy
if aspirate is not adequate), blood draw for correlative studies using
peripheral blasts, quality of life questionnaire (FACT-Leu), hematology (CBC
with differential), selinexor dosing or physician's choice treatment, PK
sampling, PD sampling, baseline symptoms, oxygen saturation, nutritional
consultation, antineoplastic therapy and adverse event assessments, daily
registration of body temperature during treatment until 30 days after
termination of treatment..
Study burden and risks
Very common side effects (*20% or more than 1 out of 5 subjects):
* Nausea
* Anorexia - loss of appetite
* Fatigue
* Vomiting
* Weight loss
* Thrombocytopenia - low platelets
* Anemia - decrease in red blood cells
Less common (<20% or less 1 out of 5 subjects):
* Diarrhea
* Dysguesia - change in taste
* Dizziness
* Dehydration
* Constipation
* Dry mouth
* Changes in vision including blurred vision
* Decrease in neutrophils - a type of white blood cell that helps fight
infections
* Decrease in white blood cells
* Low sodium
Rare side effects (*5% or less than 1 out of 20 subjects):
* worsening of pre-existing cataracts
* acute cerebellar syndrome * symptoms can include a sudden loss of
coordination, balance, or slurred speech.
* Infection
* Sepsis * potentially life-threatening complication of an infection that has
spread via the bloodstream.
* Pneumonia or inflammation of lung(s)
Franziska-Bilek-Weg 9
Munich D-80339
DE
Franziska-Bilek-Weg 9
Munich D-80339
DE
Listed location countries
Age
Inclusion criteria
Patients age * 60 years with relapsed/refractory AML (defined using WHO criteria) of any type except for acute promyelocytic leukemia (APL; AML M3), who have poor prognosis (intermediate or adverse risk) cytogenetics, with relapsed or refractory AML, after at least one prior AML therapy (must have included an adequate trial of a hypomethylating agent with at least 2 cycles), who have never undergone, and who are not currently eligible for stem cell transplantation, and are currently deemed unfit for intensive chemotherapy.
Exclusion criteria
Patients with AML M3, known central nervous system (CNS) leukemia, who are in blast transformation of chronic myeloid leukemia (CML), or whose AML is classified as favorable according to the European LeukemiaNet (ELN) disease risk assessment will be excluded from this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-000920-26-NL |
| CCMO | NL48882.029.14 |