Recurrent Adult Acute Myeloid Leukemia
Conditions
Brief summary
This phase I trial studies the side effects and best dose of ibrutinib when given together with idarubicin and cytarabine in treating patients with acute myeloid leukemia that has returned after a period of improvement or has not responded to previous treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib together with idarubicin and cytarabine may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES: Identify the safety and recommended phase 2 dose of ibrutinib in combination with idarubicin/cytarabine in relapsed/refractory acute myeloid leukemia (AML). SECONDARY OBJECTIVES: * Assess the induction response rate (complete remission \[CR\]/complete remission with incomplete count \[CRi\]) of ibrutinib in combination with idarubicin/cytarabine in relapsed/refractory AML. * Assess overall survival of ibrutinib in combination with idarubicin/cytarabine in relapsed/refractory AML. OUTLINE: This is a dose-escalation study of ibrutinib. INDUCTION: Patients receive ibrutinib orally (PO) once daily (QD) on days 1 to 21, idarubicin intravenously (IV) over 15 minutes on days 1 to 3 and cytarabine IV continuously on days 1 to 4. CONSOLIDATION: Patients achieving CR or CRi may receive ibrutinib PO QD on days 1 to 21, idarubicin IV over 15 minutes on Days 1and 2 and cytarabine IV continuously on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients maintaining a CR/CRi may receive ibrutinib PO QD on days 1 to 28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 6 months.
Interventions
DRUGCytarabine
Given IV
DRUGIbrutinib
Given PO
DRUGIdarubicin
Given IV
Sponsors
National Cancer Institute (NCI)
Steven E. Coutre
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previous morphologically-confirmed diagnosis of acute myeloid leukemia (AML) based on World Health Organization (WHO) Criteria * At least one prior chemotherapy regimen to treat AML * Disease relapse or refractory disease as shown by \> 5% blasts in the bone marrow (not attributable to another cause). Administration of hydrea to control high WBC count is permitted. * Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, or Karnofsky Performance Status (KPS) ≥ 60% * Life expectancy \> 4 weeks * Platelet count ≥ 10,000/mm3 within 72 hours of initiating the Induction Cycle (platelet transfusion support is allowed) * Serum creatinine ≤ 2.0 mg/dL within 72 hours of initiating the Induction Cycle * Total bilirubin ≤ 2.1 mg/dL within within 72 hours of initiating the Induction Cycle (EXCEPTION: If elevation is not due to liver dysfunction, and is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome, or hemolysis of non-hepatic origin) * Serum glutamic oxaloacetic transaminase (SGOT) \[aspartate aminotransferase (AST) \] ≤ 3.0 X upper limit of normal (ULN) within 72 hours of initiating the Induction Cycle * Serum glutamic pyruvic transaminase (SGPT) \[alanine aminotransferase (ALT)\] ≤ 3.0 X ULN within 72 hours of initiating the Induction Cycle * Baseline prothrombin time (PT)/international normalized ratio (INR) ratio \< 3 X ULN within 7 days of initiating the Induction Cycle (for subjects with correctable coagulation abnormalities, coagulation factor support per institutional standard of care for AML is allowed) * Partial thromboplastin time (PTT) \< 3 X ULN within 7 days of initiating the Induction Cycle (for subjects with correctable coagulation abnormalities, coagulation factor support per institutional standard of care for AML is allowed) * Negative pregnancy test within 14 days prior to study treatment (for Women of reproductive potential only) * Women of child-bearing potential and men must agree (in ICF) to use adequate contraception (eg, hormonal or barrier methods of birth control; abstinence; sterilized partner) for the duration of study participation * Ability to understand and the willingness to sign the written informed consent document
Exclusion criteria
* Received anticancer therapy (chemotherapy, immunotherapy, radiotherapy, or investigational therapy) within 2 weeks prior to starting study treatment \[EXCEPTION: Hydroxyurea (hydrea) to control high white blood cell count is permitted\] * Receiving any other investigational agents within 14 days or 5 effective half lives (whichever is shorter) prior to 1st dose of ibrutinib * Prior treatment with ibrutinib * Known unresolved toxicities due to prior anticancer therapy \[≥ Grade 2, by Common Terminology Criteria for Adverse Events (CTCAE) v4.03\] unless otherwise defined in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Response Rate | 12 weeks | The induction Response Rate (CR/CRi) of ibrutinib in combination with idarubicin/cytarabine in relapsed/refractory AML was assessed as the number of participants who achieving a complete response (CR) or complete response with incomplete blood count recovery (CRi), divided by the total number of participants completing induction therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 6 months | Overall survival (OS) was assessed as the number of patients remaining alive 6 months after the initiation of study therapy |
Countries
United States
Outcome results
None listed