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

NCT02582359 | Completed Phase 1 DMC

• 1 other identifier: 15-276
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

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

  Safety of MLN9708 in induction

  1 year

• MTD/RP2D of MLN9708 with combination with consolidation chemotherapy

  Safety of MLN9708 in consolidation tested separately

  1 year

Secondary Outcomes (5)

• Dose Limiting Toxicities of MLN9708

  1 year

• Disease Free Survival (DFS)

  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

• Overall Survival (OS)

  2 Years

• Remission Rate

  2 years

• Relationship between CD74 expression and remission, DFS, OS

  2 Years

Study Arms (1)

MLN9708

EXPERIMENTAL

Phase 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

Drug: MLN9708; Drug: Cytarabine; Drug: Daunorubicin

Interventions

MLN9708 DRUG

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.

Also known as: Ixazomib

MLN9708

Cytarabine DRUG

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

Also known as: Cytosar-U®, Ara-C, Arabinosylcytosine

MLN9708

Daunorubicin DRUG

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

Also known as: Cerubidine®

MLN9708

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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.
• 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 \[AML with t(15;17)\]

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ixazomib; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Philip C Amrein, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Philip C. Amrein, MD

Study Record Dates

• First Submitted: October 18, 2015
• First Posted: October 21, 2015
• Study Start: January 1, 2016
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: August 24, 2022

Record last verified: 2022-08

Locations

US (1)