Recurrent Adult Acute Myeloid LeukemiaPhase 1NCT02635074
Ibrutinib, Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 1 study testing Cytarabine, Ibrutinib and Idarubicin in people with Recurrent Adult Acute Myeloid Leukemia, run by Steven E. Coutre at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Adult Acute Myeloid Leukemia
- What is being tested?
- Cytarabine, Ibrutinib and Idarubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to 10 Nov 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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/exclusion criteria (EXCEPTION: alopecia)
- Known acute promyelocytic leukemia (French-American-British Class M3-AML)
- Known active central nervous system (CNS) leukemia
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- Prior bone marrow transplant presenting with active uncontrolled graft vs host disease (GvHD)
- Known congenital bleeding disorders, such as hemophilia
- Known history of stroke or intracranial hemorrhage within 6 months prior to study treatment
- Concomitant use of warfarin or other vitamin K antagonists
- Requires treatment with strong CYP3A inhibitors at the time of study enrollment. Washout period is 5 effective half-lives is required prior to 1st dose of ibrutinib
- Requires treatment with strong CYP3A inducers at the time of study enrollment. Washout period is 5 effective half-lives is required prior to 1st dose of ibrutinib
- Known active uncontrolled systemic infection
- Major surgery within 4 weeks of 1st dose of ibrutinib
- Unable to swallow capsules
- Known Malabsorption syndrome
- Known Disease significantly affecting gastrointestinal function
- Resection of the stomach or small bowel
- Uncontrolled symptomatic inflammatory bowel disease
- Ulcerative colitis
- Bowel obstruction, partial or complete
- Congestive heart failure with ejection fraction (EF) < 45%
- Uncontrolled cardiac disease, including uncontrolled cardiac arrhythmia or coronary artery disease (CAD) with active symptoms due to CAD defined as unstable angina
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib; idarubicin; or cytarabine
- Uncontrolled intercurrent illness including, but not limited to:
- Active infection
- Psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant
- Lactating
- Known positive HIV
- Known active hepatitis C
- Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University, School of Medicine
Palo Alto, California, 94304
About this study
Official title: A Phase I Dose Escalation Study of Ibrutinib With Idarubicin/Cytarabine for Relapsed/Refractory Acute Myeloid Leukemia
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.
Read the 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.
- Conditions
- Recurrent Adult Acute Myeloid Leukemia
- Being tested
- Cytarabine, Ibrutinib, Idarubicin
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytarabineDrug
Also called Beta-cytosine arabinoside, 1-beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-beta-D-arabinofuranosylcytosine, 2(1H)-pyrimidinone, 4-amino-1-beta-d-arabinofuranosyl
Given IV
IbrutinibDrug
Also called Imbruvica, BTK Inhibitor PCI-32765, PCI-32765, CRA-032765
Given PO
IdarubicinDrug
Also called Idamycin, Zavedos, 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ibrutinib, idarubicin, cytarabine) | Experimental | INDUCTION: Ibrutinib daily 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 daily on days 1 to 21, idarubicin IV over 15 minutes on days 1 to 2 and cytarabine IV continuously on days 1 to 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 daily on days 1 to 28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cytarabine; Drug: Ibrutinib; Drug: Idarubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Induction Response Rate
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.
Measured: 12 weeks
Secondary outcomes (1)
Overall Survival (OS)
Overall survival (OS) was assessed as the number of patients remaining alive 6 months after the initiation of study therapy
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2015 (estimated)
- Study startNov 2016
- Primary completion18 Jul 2017
- Study completion10 Nov 2017
Why it stopped: safety
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Adult Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steven E. Coutre
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Steven E. Coutre, Stanford University
- Investigators
- Steven Coutre, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02635074
- Sponsor's protocol ID
- HEMAML0036
- Other IDs
- NCI-2015-01961, 35003, IRB-35003, P30CA124435
- Status last verified
- May 2018
- First submitted
- 16 Dec 2015
- Last updated
- 14 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of Ibrutinib With Idarubicin/Cytarabine for Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT02635074
- Acronym / sponsor ID
- HEMAML0036
- Conditions
- Recurrent Adult Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: safety
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Steven E. CoutreUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2016
- Primary completion
- 18 Jul 2017 (actual)
- Study completion
- 10 Nov 2017 (actual)
- First posted
- 18 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ibrutinib, idarubicin, cytarabine) | Experimental | Drug: Cytarabine, Drug: Ibrutinib, Drug: IdarubicinINDUCTION: Ibrutinib daily 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 daily on days 1 to 21, idarubicin IV over 15 minutes on days 1 to 2 and cytarabine IV continuously on days 1 to 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 daily on days 1 to 28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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%
Key exclusion criteria (32 listed)
- 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/exclusion criteria (EXCEPTION: alopecia)
- Known acute promyelocytic leukemia (French-American-British Class M3-AML)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytarabineAlso: Beta-cytosine arabinoside, 1-beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-beta-D-arabinofuranosylcytosine, 2(1H)-pyrimidinone, 4-amino-1-beta-d-arabinofuranosylGiven IV | Drug | Treatment (ibrutinib, idarubicin, cytarabine) |
| IbrutinibAlso: Imbruvica, BTK Inhibitor PCI-32765, PCI-32765, CRA-032765Given PO | Drug | Treatment (ibrutinib, idarubicin, cytarabine) |
| IdarubicinAlso: Idamycin, Zavedos, 4-Demethoxydaunomycin, 4-DemethoxydaunorubicinGiven IV | Drug | Treatment (ibrutinib, idarubicin, cytarabine) |
Primary outcome
Induction Response Rate
Time frame: 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.
1 secondary outcome
Overall Survival (OS)
Time frame: 6 months
Results and safety
The study was stopped early (reason given: safety). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Coutre principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cytarabine, Ibrutinib and Idarubicin in people with Recurrent Adult Acute Myeloid Leukemia, run by Steven E. Coutre at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: safety). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Induction Response Rate (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2018.