Adult Acute Megakaryoblastic Leukemia (M7)Phase 2NCT02030405
Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 2 study testing Ixazomib in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Steven E. Coutre at 1 site in United States.
Trial summary
This phase 2 trial studies how well ixazomib(MLN9708) works in treating study participants with relapsed or refractory acute myeloid leukemia. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)
- What is being tested?
- Ixazomib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Nov 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of relapsed or refractory AML of any French American British (FAB) subtype except M3 and NPM1 genetic mutation detected by molecular assay; AML patients treated at Stanford have NPM1 molecular mutation status checked routinely at time of diagnosis in a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory
- Male or female patients and no race-ethnic restrictions
- Patients are unwilling, or who are determined to be medically unfit for or resistant to standard intensive induction chemotherapy; patients who are medically unfit will be determined by the treating primary hematologist and the principal investigator (including but not limited to evaluation of co-morbidities, and response and complications to previous AML treatment strategy)
- Eastern Cooperative Oncology Group (ECOG) 0 to 2
- Ability to understand and the willingness to sign a written informed consent document
- Female patients who:
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- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
- Calculated creatinine clearance ≥ 30 mL/min
Who cannot join
- Female patient who are lactating or have a positive serum pregnancy test during the screening period
- Major surgery within 14 days before enrollment
- Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of MLN9708
- Known active and uncontrolled central nervous system (CNS) involvement of leukemia (a lumbar puncture does not need to be performed as a part of screening)
- Have a significant uncontrolled infection active infection
- Have other severe concurrent disease or serious organ dysfunction involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
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- Systemic treatment, within 14 days before the first dose of MLN9708, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
- Known ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty
- Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection; this does not preclude previous diagnosis of acute myeloid leukemia or myelodysplastic syndrome
- Patient has ≥ grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening
- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Cancer Institute
Stanford, California, 94305
About this study
Official title: A Phase 2 Study of Single-Agent MLN9708 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia With Mutated Nucleophosmin-1
This phase 2 trial studies how well ixazomib(MLN9708) works in treating study participants with relapsed or refractory acute myeloid leukemia. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVE:
Determine the best response including complete remission (CR), CR with incomplete recovery (CRi), and partial remission (PR) after 3 cycles of treatment with MLN9708 (ixazomib) in participants with nucleophosmin (NPM)1-mutated acute myeloid leukemia (AML) (following the LeukemiaNet1 guidelines for response criteria).
SECONDARY OBJECTIVES:
- Determine the duration of remission in all responders after treatment with MLN9708 defined as the time of documented remission until relapse.
- Determine the 1 year overall survival, which will be measured from time of study entry to the earlier of death from any cause or end of follow up at 1 year.
- Establish toxicity and tolerability of MLN9708 treatment in AML, including non-hematologic toxicities grade 3 or above as specified by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
OUTLINE:
Participants receive ixazomib orally (PO) on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
- Conditions
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Being tested
- Ixazomib
- Medical subject headings
- Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxazomibDrug
Also called Ninlaro, MLN9708, proteasome inhibitor
Given orally (PO)
| Study group | Role | What they receive |
|---|---|---|
| Ixazomib (MLN9708) | Experimental | Participants receive ixazomib PO (orally) on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Ixazomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Overall response rate after 3 cycles of treatment (9 weeks) was assessed as complete remission (CR); CR with incomplete recovery (CRi); and partial remission (PR) with MLN9708, in participants with NPM1-mutated AML by LeukemiaNet1 guidelines:
Although achievement of complete remission (CR) has unique clinical significance for improved overall survival (OS) and relapse-free survival (RFS) compared to achievement of CRi with incomplete platelet recovery, the latter is still a clinically meaningful response, as it is independently-superior to resistant disease.
Partial remission (PR) is defined as meeting all hematologic criteria for CR with an allowance for 5% to 25% bone marrow blasts or decrease of pre-treatment bone marrow blast percentage by at least 50%.
Stable disease is defined as a change in bone marrow aspirate blast count within 10% of baseline.
Relapsed disease is defined as reappearance of blasts in the blood or bone marrow blasts
Measured: 9 weeks
Secondary outcomes (3)
Duration of Response (DOR)
Duration of response (DOR) in participants with complete remission (CR) was defined as the period of time from documented complete remission through relapse or death, with relapse defined as reappearance of blasts in the blood or bone marrow blasts, after documented CR. DOR was to be assessed through at least 1 year follow-up.
Measured: 1 year
Overall Survival (OS)
Overall survival (OS) from time of study entry to the earlier of death from any cause or end of follow up at 1 year
Measured: 1 year
Serious Adverse Events Related to Ixazomib
Ixazomib toxicity and tolerability were assessed based on the non-hematologic toxicities ≥ Grade 3 determined to be possibly, probably, or definitely related to the study agent Ixazomib.
Adverse events that are possibly, probably, or definitely related to the study agent are considered "toxicities." The outcome is reported as the overall number of non-hematologic toxicities ≥ Grade 3.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2014 (estimated)
- Study startMar 2014
- Primary completionNov 2015
- Study completionNov 2015
Why it stopped: Regulatory
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Acute Megakaryoblastic Leukemia (M7)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 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
- Bruno de Medeiros, Principal investigator, Stanford University Hospitals and Clinics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02030405
- Sponsor's protocol ID
- IRB-28771
- Other IDs
- NCI-2013-02231, P30CA124435, HEMAML0028
- Status last verified
- Apr 2019
- First submitted
- 25 Nov 2013
- Last updated
- 5 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Single-Agent MLN9708 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia With Mutated Nucleophosmin-1
- ClinicalTrials.gov ID
- NCT02030405
- Acronym / sponsor ID
- IRB-28771
- Conditions
- Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Regulatory
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Steven E. CoutreUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2014
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 8 Jan 2014 (estimated)
- Results
- Posted 10 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 2 trial studies how well ixazomib(MLN9708) works in treating study participants with relapsed or refractory acute myeloid leukemia. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVE:
Determine the best response including complete remission (CR), CR with incomplete recovery (CRi), and partial remission (PR) after 3 cycles of treatment with MLN9708 (ixazomib) in participants with nucleophosmin (NPM)1-mutated acute myeloid leukemia (AML) (following the LeukemiaNet1 guidelines for response criteria).
SECONDARY OBJECTIVES:
- Determine the duration of remission in all responders after treatment with MLN9708 defined as the time of documented remission until relapse.
- Determine the 1 year overall survival, which will be measured from time of study entry to the earlier of death from any cause or end of follow up at 1 year.
- Establish toxicity and tolerability of MLN9708 treatment in AML, including non-hematologic toxicities grade 3 or above as specified by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
OUTLINE:
Participants receive ixazomib orally (PO) on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ixazomib (MLN9708) | Experimental | Drug: IxazomibParticipants receive ixazomib PO (orally) on days 1, 4, 8, and 11. Treatment repeats every 21 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 (18 listed)
- Diagnosis of relapsed or refractory AML of any French American British (FAB) subtype except M3 and NPM1 genetic mutation detected by molecular assay; AML patients treated at Stanford have NPM1 molecular mutation status checked routinely at time of diagnosis in a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory
- Male or female patients and no race-ethnic restrictions
- Patients are unwilling, or who are determined to be medically unfit for or resistant to standard intensive induction chemotherapy; patients who are medically unfit will be determined by the treating primary hematologist and the principal investigator (including but not limited to evaluation of co-morbidities, and response and complications to previous AML treatment strategy)
- Eastern Cooperative Oncology Group (ECOG) 0 to 2
- Ability to understand and the willingness to sign a written informed consent document
Key exclusion criteria (13 listed)
- Female patient who are lactating or have a positive serum pregnancy test during the screening period
- Major surgery within 14 days before enrollment
- Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of MLN9708
- Known active and uncontrolled central nervous system (CNS) involvement of leukemia (a lumbar puncture does not need to be performed as a part of screening)
- Have a significant uncontrolled infection active infection
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 |
|---|---|---|
| IxazomibAlso: Ninlaro, MLN9708, proteasome inhibitorGiven orally (PO) | Drug | Ixazomib (MLN9708) |
Primary outcome
Overall Response Rate (ORR)
Time frame: 9 weeks
Overall response rate after 3 cycles of treatment (9 weeks) was assessed as complete remission (CR); CR with incomplete recovery (CRi); and partial remission (PR) with MLN9708, in participants with NPM1-mutated AML by LeukemiaNet1 guidelines: Although achievement of complete remission (CR) has unique clinical significance for improved overall survival (OS) and relapse-free survival (RFS) compared to achievement of CRi with incomplete platelet recovery, the latter is still a clinically meaningful response, as it is independently-superior to resistant disease. Partial remission (PR) is defined as meeting all hematologic criteria for CR with an allowance for 5% to 25% bone marrow blasts or decrease of pre-treatment bone marrow blast percentage by at least 50%. Stable disease is defined as a change in bone marrow aspirate blast count within 10% of baseline. Relapsed disease is defined as reappearance of blasts in the blood or bone marrow blasts
3 secondary outcomes
Duration of Response (DOR)
Time frame: 1 year
Overall Survival (OS)
Time frame: 1 year
Serious Adverse Events Related to Ixazomib
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Bruno de Medeiros principal investigator
Stanford University Hospitals and Clinics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ixazomib in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), 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 18 inclusion and 13 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 5 Apr 2019. 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 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?
Yes. Results are posted in the registry (first posted 10 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (ORR) (time frame: 9 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 5 Apr 2019.