Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT02030405 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB-28771NCI-2013-02231P30CA124435HEMAML0028
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

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); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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

  9 weeks

Secondary Outcomes (3)

• Duration of Response (DOR)

  1 year

• Overall Survival (OS)

  1 year

• Serious Adverse Events Related to Ixazomib

  1 year

Study Arms (1)

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.

Drug: Ixazomib

Interventions

Ixazomib DRUG

Given orally (PO)

Also known as: Ninlaro, MLN9708, proteasome inhibitor

Ixazomib (MLN9708)

Eligibility Criteria

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

You may qualify if:

• 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:
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Steven E. Coutre: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University Cancer Institute

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

ixazomib; Proteasome Inhibitors

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Bruno Carneiro de Medeiros, MD
• Organization: Stanford University Medical Center

bruno.medeiros@stanford.edu

650-498-6000

Study Officials

• Bruno de Medeiros

  Stanford University Hospitals and Clinics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: January 8, 2014
• Study Start: March 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: April 5, 2019
• Results First Posted: March 10, 2017

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)