Proteasome Inhibitor MLN9708 in Treating Patients With Relapsed Multiple Myeloma That Is Not Refractory to Bortezomib

This study is currently recruiting participants.
Verified March 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01415882
First received: August 5, 2011
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

This phase II trial studies how well proteasome inhibitor MLN9708 works in treating patients with relapsed multiple myeloma that is not refractory to bortezomib. Proteasome inhibitor MLN9708 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Multiple Myeloma
Drug: proteasome inhibitor MLN9708
Drug: dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Trial of MLN9708 in Patients With Relapsed Multiple Myeloma Not Refractory to Bortezomib

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Proportion of confirmed response (stringent complete response [sCR], CR, very good partial response [VGPR], PR) with single agent proteasome inhibitor MLN9708 [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    A confirmed response is defined as sCR, CR, VGPR, or PR noted as the objective status on 2 separate evaluations while receiving single agent proteasome inhibitor MLN9708. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients.


Secondary Outcome Measures:
  • Overall response rate of MLN9708 in combination with dexamethasone by bone marrow aspirate and biopsy, myeloma FISH, metaphase cytogenetics, PCLI, and flow cytometry at 2 and 4 months. [ Time Frame: no longer than 2 years ] [ Designated as safety issue: No ]
  • Survival out to 2 years [ Time Frame: Every 6 months for 2 years ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Every 6 months for 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 103
Study Start Date: January 2012
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor, dexamethasone)
Patients receive MLN9708 PO on days 1, 8 and 15. Patients with lack of minor response by the end of the second course or lack of partial response by the end of the fourth course also receive dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: proteasome inhibitor MLN9708
Given PO
Other Names:
  • MLN2238
  • MLN9708
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the confirmed overall response rate (>= partial response [PR]) of MLN9708 (proteasome inhibitor MLN9708), used as a single agent in patients with relapsed multiple myeloma, who are proteasome inhibitor naive (including bortezomib) naive OR have received less than 6 cycles of therapy with bortezomib and had a better than PR with no progression at the time of discontinuation.

SECONDARY OBJECTIVES:

I. To determine the overall response rate of MLN9708 in combination with dexamethasone, when dexamethasone is added to MLN9708 for lack of response or for progression.

II. To determine the event free survival and overall survival among patients with relapsed myeloma following treatment with MLN9708 with dexamethasone added for lack of response or progression.

OUTLINE:

Patients receive MLN9708 orally (PO) on days 1, 8 and 15. Patients with lack of minor response by the end of the second course or lack of partial response by the end of the fourth course also receive dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 or 12 months for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Calculated creatinine clearance (using Cockcroft-Gault equation) >=30 mL/min
  • Total bilirubin <= 1.5 x the upper limit of the normal range (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3x
  • Absolute neutrophil count >= 1000/mL
  • Platelet count >= 75000/mL
  • Hemoglobin >= 8.0 g/dL
  • Patients with relapsed multiple myeloma who have already received one or more standard treatment regimens
  • Measurable disease of multiple myeloma as defined by at least ONE of the following:
  • Serum monoclonal protein >= 1.0 g/dL
  • >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
  • Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
  • Patients should be proteasome inhibitor naïve (including bortezomib) OR have received less than 6 cycles of therapy with a bortezomib containing regimen and were not refractory to the bortezomib based regimen (less than a PR or progression on or within 60 days of discontinuation)
  • Provide informed written consent
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Willing to return to Mayo Clinic enrolling institution for follow-up
  • Recovered (ie, < Grade 1 toxicity) from the reversible effects of prior antineoplastic therapy

Exclusion Criteria:

  • Recent prior chemotherapy:
  • Alkylators (e.g. melphalan, cyclophosphamide) =< 14 days prior to registration
  • Anthracyclines =< 14 days prior to registration
  • High dose corticosteroids, immune modulatory drugs (thalidomide or lenalidomide) =< 7 days prior to registration
  • Prior therapy with any proteasome inhibitor other than bortezomib
  • No concomitant high dose corticosteroids other than what is part of treatment protocol (concurrent use of corticosteroids); EXCEPTION: Patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
  • Other active malignancy =< 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
  • Any of the following:
  • Pregnant women or women of reproductive ability who are unwilling to use 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of study drug
  • Nursing women
  • Men who are unwilling to use a condom (even if they have undergone prior vasectomy) while having intercourse with any women, while taking the drug and for 30 days after stopping treatment
  • Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
  • Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
  • Patient has ≥ Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
  • Major surgery within 14 days before study registration
  • Systemic treatment with strong inhibitors of cytochrome P450 1A2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450 3A4 (CYP3A4) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, Gingko biloba, St. John's wort) within 14 days before the first dose of MLN9708
  • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months; Note: Prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
  • Known human immunodeficiency virus (HIV) positive
  • Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
  • 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
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing
  • Diarrhea > Grade 1, based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading, in the absence of antidiarrheals
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01415882

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Craig B Reeder, MD         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Vivek Roy, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Shaji K. Kumar, MD         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Shaji Kumar, M.D. Mayo Clinic
Principal Investigator: Craig B. Reeder, M.D. Mayo Clinic
Principal Investigator: Vivek Roy, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Kumar, Shaji, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT01415882     History of Changes
Other Study ID Numbers: MC1181, NCI-2011-02303, MC1181, 11-001516
Study First Received: August 5, 2011
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on April 22, 2014