Clinical trial NCT02249091: A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
Official title: An Investigator-Initiated Study To Evaluate Ara-C and Idarubicin in Combination With the Selective Inhibitor Of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Relapsed Or Refractory AML
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (Relapsed/Refractory)
Lead sponsor: GSO Global Clinical Research BV
Sponsor class: OTHER
Collaborators: name: Karyopharm Therapeutics Inc
First posted: 2014-09-25
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: In the initial protocol, 25 patients are included in the clinical trial on the schedule described as cohort 1. After an amendment 15 further patients are included on the schedule described as cohort 2.
Primary purpose: TREATMENT

Brief summary: Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several drugs with different ways of inhibiting the cell growth. In this trial, standard chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will be combined with a new drug called Selinexor.

Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus which control the cell growth.


Eligibility criteria: Inclusion Criteria:

1. Cytological or histological diagnosis of AML with the exception of promyelocytic leukemia (AML M3)
2. Patients must have relapsed/refractory disease (relapse after stem cell transplantation is permitted) as defined as:

   1. patients with \<PR after first cycle of induction chemotherapy, or
   2. patients with \<CR(i) after second cycle of induction chemotherapy, or
   3. patients who relapse after conventional chemotherapy or
   4. patients who have undergone a single stem cell transplantation and who have relapse of their AML.
3. Men and women aged ≥18 years and eligible for standard dose of chemotherapy (7+3);
4. A period of at least 3 weeks needs to have elapsed since last treatment (with the exception of hydroxyurea) before participating in this study. Hydroxyurea induction therapy to reduce peripheral blast counts is permitted prior to initiation of treatment on protocol. Treatment may begin in \<3 weeks from last treatment if deemed in the best interest of the patient after discussion with the PI of the study;
5. ECOG performance status ≤ 2
6. Serum biochemical values with the following limits unless considered due to leukemia: creatinine ≤2 mg/dl; total bilirubin ≤2x ULN, unless increase is due to hemolysis or congenital disorder; transaminases (SGPT or SGOT) ≤2.5x ULN.
7. Ability to swallow and retain oral medication;
8. Ability to understand and provide signed informed consent;
9. Cardiac ejection fraction must be \>/=50% (by echocardiography).
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Treatment with any investigational agent within four weeks.
2. Cumulative anthracycline dose (daunorubicin or equivalent) \>360 mg/m\^2
3. HIV infection
4. Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to:
5. Presence of CNS leukemia
6. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery.
7. For patients after SCT as part of prior treatment:

   1. Necessity of immunosuppressive drugs
   2. GvHD \> grade 1
8. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.
9. Ongoing cardiac dysrhythmias of NCI CTCAE \>/= Grade 2.
10. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
11. Clinically significant bleeding within 1 month

Primary outcomes:
measure: Number of Participants With CR/CRi = Overall Reponse Rate
timeFrame: 1-2 induction cycles (4 - 8 weeks)
Secondary outcomes:
measure: Number of Participants With Partial Remission (PR) = Rate of PR
timeFrame: 1-2 induction cycles (4 - 8 weeks)
measure: Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)
timeFrame: 1-2 induction cycles (4 - 8 weeks)
measure: Early Death Rate
timeFrame: 1 induction cycle (4 weeks)
measure: Overall Survival
timeFrame: Time from registration to event, max 2 years
measure: Relapse-Free Survival
timeFrame: Time from registration to event, max 2 years
measure: Event-Free Survival
timeFrame: Time from registration to event, max 2 years
measure: Progression-Free Survival
timeFrame: Time from registration to event, max 2 years
Other outcomes:
Locations:
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
Study officials:
References: