Acute Myeloid LeukemiaPhase 1/2NCT02303782
A Study Assessing tOTX015 in Combination With Azacitidine (AZA) or AZA Single Agent in Patients With Newly-diagnosed Acute Myeloid Leukemia (AML) Not Candidate for Standard Intensive Induction Therapy (SIIT)
A Phase 1/2 study testing OTX015 and Vidaza (azacitidine) in people with Acute Myeloid Leukemia, run by Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
Trial summary
This study is designed in its first part (phase Ib) to determine the recommended dose of the OTX015 + Vidaza (azacitidine) combination in newly diagnosed acute myeloid leukemia patients not candidate for standard intensive induction therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- OTX015 and Vidaza (azacitidine)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2015to Mar 2016
- Phase
- Phase 1/2
- 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
- Signed informed consent prior to beginning protocol-specific procedures. Patients registered for this trial must be treated and followed at the participating centers.
- Newly-diagnosed confirmed AML, defined as > 20% myeloid blasts in the bone marrow.
- Patients not candidate for standard intensive induction therapy (SIIT) with anthracycline and cytarabine (3+7) due to age, and/or poor general condition, and/or comorbidities, and/or any condition predicting a poor benefit/risk ratio of such chemotherapy, including complex karyotypes or secondary AML (including those with myelodysplastic features and 20-30% bone marrow blasts, who are already standard indication for AZA single agent therapy). There is no upper age limit and no protocol definition of co-morbidities. The decision that the patient is not candidate for SIIT will be made by the investigator team according to routine daily practice, based on the combination of these parameters and patient preference. The reasons for non-eligibility for SIIT will be documented in the inclusion procedures to characterize the treated population.
- Patients > 18 years old.
- Life expectancy of at least 3 months.
- ECOG performance status (PS) of 0 to 2. Patients with PS > 2 at the time of diagnosis may still be enrolled, provided their PS improves to ≤2 after hematologic supportive care (transfusions, antibiotics, hydration, correction of metabolic disturbances, correction of hyperleukocytosis with hydroxyurea).
Show all 11Show fewer
- Patients should not have previously received other anti-leukemia drugs, except hydroxyurea (± mercaptopurine [6MP] or thioguanine [6TG]), given to control rapidly increasing hyperleukocytosis. Hydroxyurea (±6MP or 6TG) must be stopped at least 48 hours prior to start study treatment. It may be resumed to control hyperleukocytosis from Day 3 to 57. Patients who still need hydroxyurea (± 6MP or 6TG) beyond Day 57 (or end of cycle 2 in case of treatment delay) should be considered as having treatment failure.
- Calculated creatinine clearance (CrCl) < 30 mL/min (Cockroft \& Gault formula, or MDRD formula for patients aged > 65 years). Patients with CrCl < 60 mL/min should be considered at risk for increased hematologic toxicity and renal toxicity.
- Adequate LFTs: Total bilirubin ≤ the institutional upper limit of normal (ULN); ALAT/ASAT > 3 x ULN (or > 5 x ULN in case of leukemic liver involvement).
- Serum albumin > 28 g/L.
- Complete baseline disease assessment workup (including routine cytogenetics and centralized assessment of molecular biomarkers) prior to the first study treatment administration.
Who cannot join
- Pregnant or lactating women or women of childbearing potential not using adequate contraception. Male patients not using adequate contraception.
- Patients with acute promyelocytic leukemia, or uncontrolled symptomatic disseminated intravascular coagulation (DIC).
- Increasing or stable hyperleukocytosis > 15 G/L despite optimal hydroxyurea dose (± 6MP or 6TG).
- Uncontrolled disease-related metabolic disorder.
- Patients unable to swallow oral medication or with a gastrointestinal condition (e.g. malabsorption, resection) deemed to jeopardize intestinal absorption of OTX015.
- Other serious illness or medical condition, which in the investigator's opinion could hamper understanding of the study by the patient, patient's compliance to study treatment, patient's safety or interpretation of study results. These conditions include (but are not restricted to):
Show all 12Show fewer
- Congestive heart failure or angina pectoris except if medically controlled, previous history of myocardial infarction within 1 year of study entry, uncontrolled hypertension or arrhythmias.
- Significant neurologic or psychiatric disorders impairing ability to obtain consent.
- Second cancer, needing systemic therapy.
- Known HIV positivity, hepatitis B positivity by surface antigen expression, or active hepatitis C infection (PCR positive or antiviral therapy for hepatitis C within last 6 months).
- Concomitant therapy with strong CYP3A4 interfering drugs.
- Concurrent treatment with other experimental therapies or participation in another clinical trial within 21 days prior to first study treatment administration or 5 half-lives of previously administered drugs, whichever is longer, or previous anti-leukemic therapy other than hydroxyurea (± 6MP or 6TG).
About this study
Official title: A Phase Ib/II Study Assessing the BET-bromodomain (BRD) Inhibitor OTX015 in Combination With Azacitidine (AZA) or AZA Single Agent in Patients With Newly-diagnosed Acute Myeloid Leukemia (AML) Not Candidate for Standard Intensive Induction Therapy (SIIT)
This study is designed in its first part (phase Ib) to determine the recommended dose of the OTX015 + Vidaza (azacitidine) combination in newly diagnosed acute myeloid leukemia patients not candidate for standard intensive induction therapy.
It will be followed by a randomized phase II part to assess the efficacy of the combination using 2 arms : Vidaza (azacitidine) alone vs. OTX015 in combination with Vidaza (azacitidine).
- Conditions
- Acute Myeloid Leukemia
- Being tested
- OTX015, Vidaza (azacitidine)
- 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.
OTX015Drug
Vidaza (azacitidine)Drug
| Study group | Role | What they receive |
|---|---|---|
| OTX015 + azacitidine | Experimental | Not described Receives: Drug: OTX015; Drug: Vidaza (azacitidine) |
| Azacitidine | Experimental | Not described Receives: Drug: Vidaza (azacitidine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity occurrence for determination of Maximum Tolerated Dose
Measured: First 28 days
Complete Remission rate
Measured: at day 29
Complete Remission rate
Measured: at day 57
Complete Remission Rate
Measured: at day 115
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionMar 2016 (estimated)
- Study completionMar 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02303782
- Sponsor's protocol ID
- 8628-004
- Other IDs
- OTX015_206
- Status last verified
- Aug 2016
- First submitted
- 24 Nov 2014
- Last updated
- 1 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study Assessing the BET-bromodomain (BRD) Inhibitor OTX015 in Combination With Azacitidine (AZA) or AZA Single Agent in Patients With Newly-diagnosed Acute Myeloid Leukemia (AML) Not Candidate for Standard Intensive Induction Therapy (SIIT)
- ClinicalTrials.gov ID
- NCT02303782
- Acronym / sponsor ID
- 8628-004
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- Jan 2015
- Primary completion
- Mar 2016 (estimated)
- Study completion
- Mar 2016 (estimated)
- First posted
- 1 Dec 2014 (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 study is designed in its first part (phase Ib) to determine the recommended dose of the OTX015 + Vidaza (azacitidine) combination in newly diagnosed acute myeloid leukemia patients not candidate for standard intensive induction therapy.
It will be followed by a randomized phase II part to assess the efficacy of the combination using 2 arms : Vidaza (azacitidine) alone vs. OTX015 in combination with Vidaza (azacitidine).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OTX015 + azacitidine | Experimental | Drug: OTX015, Drug: Vidaza (azacitidine) |
| Azacitidine | Experimental | Drug: Vidaza (azacitidine) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed informed consent prior to beginning protocol-specific procedures. Patients registered for this trial must be treated and followed at the participating centers.
- Newly-diagnosed confirmed AML, defined as > 20% myeloid blasts in the bone marrow.
- Patients not candidate for standard intensive induction therapy (SIIT) with anthracycline and cytarabine (3+7) due to age, and/or poor general condition, and/or comorbidities, and/or any condition predicting a poor benefit/risk ratio of such chemotherapy, including complex karyotypes or secondary AML (including those with myelodysplastic features and 20-30% bone marrow blasts, who are already standard indication for AZA single agent therapy). There is no upper age limit and no protocol definition of co-morbidities. The decision that the patient is not candidate for SIIT will be made by the investigator team according to routine daily practice, based on the combination of these parameters and patient preference. The reasons for non-eligibility for SIIT will be documented in the inclusion procedures to characterize the treated population.
- Patients > 18 years old.
- Life expectancy of at least 3 months.
Key exclusion criteria (12 listed)
- Pregnant or lactating women or women of childbearing potential not using adequate contraception. Male patients not using adequate contraception.
- Patients with acute promyelocytic leukemia, or uncontrolled symptomatic disseminated intravascular coagulation (DIC).
- Increasing or stable hyperleukocytosis > 15 G/L despite optimal hydroxyurea dose (± 6MP or 6TG).
- Uncontrolled disease-related metabolic disorder.
- Patients unable to swallow oral medication or with a gastrointestinal condition (e.g. malabsorption, resection) deemed to jeopardize intestinal absorption of OTX015.
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 |
|---|---|---|
| OTX015 | Drug | OTX015 + azacitidine |
| Vidaza (azacitidine) | Drug | Azacitidine, OTX015 + azacitidine |
Primary outcome
Dose Limiting Toxicity occurrence for determination of Maximum Tolerated Dose
Time frame: First 28 days
Complete Remission rate
Time frame: at day 29
Complete Remission rate
Time frame: at day 57
Complete Remission Rate
Time frame: at day 115
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OTX015 and Vidaza (azacitidine) in people with Acute Myeloid Leukemia, run by Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
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 11 inclusion and 12 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: withdrawn, as of the sponsor's last update on 1 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 withdrawn before enrolling participants, so there are no results.
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?
Dose Limiting Toxicity occurrence for determination of Maximum Tolerated Dose (time frame: First 28 days). The study lists 4 primary outcomes in all. 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 1 Sep 2016.