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Acute Myeloid LeukemiaPhase 1NCT02582359

MLN 9708 in Induction and Consolidation for Adults With AML >= 60 Years of Age

A Phase 1 study testing MLN9708, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This research study is evaluating drugs called Millennium 9708 (referred to as MLN9708) in combination with standard therapy for acute myeloid leukemia (AML) consisting of daunorubicin and cytarabine as a possible treatment for the patient AML. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
MLN9708, Cytarabine and Daunorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
1 siteUnited States
Study dates
Jan 2016to Apr 2022
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 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients 60 years or older.
  • Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  • Female patients who:
  • 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
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  • 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 (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.]
  • Patients must have a diagnosis of AML according to the World Health Organization (WHO) criteria. Therapy-related and secondary AML (arising after a period of myelodysplasia [MDS]) allowed. Prior treatment for MDS with hypomethylator-based therapy and lenalidomide allowed, but not allowed if used after the diagnosis of AML is made, since enrollment to this study is not for relapsed AML.
  • Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2. Performance status of 3 permissible if related to disease.
  • Patients must meet the following clinical laboratory criteria:
  • Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN) unless related to disease or patient known to have underlying Gilbert's disease.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 ULN.
  • Calculated creatinine clearance ≥ 30 mL/min (see Section 12.2).

Who cannot join

  • Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  • Failure to have fully recovered (ie, ≤Grade 1 toxicity) from the reversible effects of prior chemotherapy as stated in Section 5.1.4.
  • 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 the MLN9708.
  • Suspected AML-related central nervous system involvement. A lumbar puncture (LP) is not required to exclude central nervous system (CNS) disease.
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
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  • Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing.
  • 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 non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • Patient has ≥ Grade 1 neuropathy, sensory, with or without pain, motor, or autonomic, on clinical examination during the screening period.
  • Participation in other clinical trials involving investigational agents within 21 days of the start of this trial and throughout the duration of this trial.
  • Prior chemotherapy treatment for AML (Prior treatment with hydroxyurea and/or leukapheresis to control white blood cell count acceptable). Prior chemotherapy for MDS or myeloproliferative neoplasms (MPN) such as azacitidine, decitabine, and thalidomide, is permitted, but such treatments once MDS or MPN has transformed to AML is not permitted.
  • Acute promyelocytic leukemia(APL) by WHO criteria [AML with t(15;17)]
  • Cardiac ejection fraction (EF) < 40%
  • Systemic treatment, during or within 48 hours of the first dose of MLN9708, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of 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. The washout period will be extended to 2 days if patients are receiving extended release ciprofloxacin. For this protocol prophylactic antibiotics are not recommended, at least not until 48 hours after the last dose of study drug (given on Day 12), when the patient may be neutropenic. For patients with fever and/or infections, cefepime and ambisome are acceptable.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Phase I Dose Escalation Study of Millennium 9708 in Combination With Induction and Consolidation Chemotherapy in Adults >= 60 Years With Acute Myeloid Leukemia

This research study is evaluating drugs called Millennium 9708 (referred to as MLN9708) in combination with standard therapy for acute myeloid leukemia (AML) consisting of daunorubicin and cytarabine as a possible treatment for the patient AML.

Read the detailed description

This research study is a clinical trial comprised of two Phase I portions an induction treatment (initial treatment), and a consolidation treatment (which is given later). The patient is being asked to participate in one or both phase I portions of this study.

A phase I study tests the safety of an investigational drug or combination of drugs. Phase I studies also try to define the appropriate dose of the investigational drugs to use for further studies. "Investigational" means that the drug combination is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved the drug combination for the participant's type of cancer.

In this research study, the investigators are studying the safety and tolerability of MLN9708 in combination with standard treatment for adults 60 years of age or older with AML.

In the first phase I portion of treatment ("induction") participants will receive MLN9708 in combination with daunorubicin and cytarabine. Once the maximally tolerated dose (MTD) of MLN9708 is established in this induction portion, up to 36 additional participants will be enrolled in the portion focusing on consolidation.

The drugs daunorubicin and cytarabine have been approved by the FDA (U.S. Food and Drug Administration). MLN9708 is not approved by the FDA.

Being tested
MLN9708, Cytarabine, Daunorubicin
Keywords
Acute Myeloid Leukemia
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.

  • MLN9708Drug

    Also called Ixazomib

    Dose of 1.5 mg or 2.3 mg or 3.0 mg taken by mouth on days 2, 5, 9, 12 of each cycle.

  • CytarabineDrug

    Also called Cytosar-U®, Ara-C, Arabinosylcytosine

    Induction: cytarabine 100 mg/m2/day continuous infusion, days 1-7 Consolidation: cytarabine 2000 mg/m2/day, 3 hour infusion, on days 1-5

  • DaunorubicinDrug

    Also called Cerubidine®

    Daunorubicin 60 mg/m2, IV bolus, on days 1-3 of induction, only.

Study groups in NCT02582359
Study groupRoleWhat they receive
MLN9708ExperimentalPhase I dose escalation study of MLN9708 with induction chemotherapy * MLN9708 -oral on predetermined days per cycle * Cytarabine, continuous infusion for predetermined duration and dosage * Daunorubicin short IV infusion or rapid injection for predetermined Phase I dose escalation study of MLN9708 with consolidation chemotherapy after establishment of MTD with induction
Receives: Drug: MLN9708; Drug: Cytarabine; Drug: Daunorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD/recommended phase 2 dose (RP2D) of MLN9708 in combination with induction chemotherapy

    Safety of MLN9708 in induction

    Measured: 1 year

  2. MTD/RP2D of MLN9708 with combination with consolidation chemotherapy

    Safety of MLN9708 in consolidation tested separately

    Measured: 1 year

Secondary outcomes (5)

  1. Dose Limiting Toxicities of MLN9708

    Generally by NCI CTCAE: grade 3 neuropathy, grade 3 non-hematological toxicity that does not resolve to grade 2, grade 4 hematological toxicity not due to persistent AML that persists

    Measured: 1 year

  2. Disease Free Survival (DFS)

    Duration in weeks or months from determination of remission to time of relapse or death

    Measured: 2 Years: Complete remission (CR) or complete remission without platelet recovery (CRp) to relapse or death, whichever comes first, for patients who receive study drug in induction and regardless of consolidation therapy

  3. Overall Survival (OS)

    Duration in weeks or months from day 1 of protocol treatment to time of death

    Measured: 2 Years

  4. Remission Rate

    Percentage of patients starting day 1 treatment that achieve a remission (CR or CRp)

    Measured: 2 years

  5. Relationship between CD74 expression and remission, DFS, OS

    Degree of CD74 expression on leukemia blasts compared to the rate of remission and length of DFS and OS.

    Measured: 2 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2015 (estimated)
  2. Study startJan 2016
  3. Primary completionApr 2022
  4. Study completionApr 2022

Resources

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
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02582359
Sponsor's protocol ID
15-276
Status last verified
Aug 2022
First submitted
18 Oct 2015
Last updated
24 Aug 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MLN9708, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia, run by Massachusetts General Hospital 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 17 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: finished, as of the sponsor's last update on 24 Aug 2022. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

MTD/recommended phase 2 dose (RP2D) of MLN9708 in combination with induction chemotherapy (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02582359.

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 24 Aug 2022.

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