Ixazomib in Treating Patients With Relapsed Multiple Myeloma That Is Not Refractory to Bortezomib

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01415882
First received: August 5, 2011
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Refractory Multiple Myeloma
Drug: ixazomib
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 responses (stringent complete response [sCR], CR, very good partial response [VGPR], PR) with single agent ixazomib (prior to initiation of dexamethasone) and with the combination of ixazomib plus dexamethasone [ Time Frame: Up to 2 years ] [ 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 ixazomib with or without dexamethasone. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method.


Secondary Outcome Measures:
  • Confirmed response rate with the addition of dexamethasone [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Estimated by the number of patients who achieve a confirmed response at any time (with single agent ixazomib or ixazomib plus dexamethasone) divided by the number of evaluable patients. 95% confidence intervals for the true confirmed response rate will be calculated by the exact binomial method.

  • Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.

  • Event-free survival [ Time Frame: From registration to disease progression while receiving ixazomib and dexamethasone, death due to any cause, or subsequent treatment for multiple myeloma, assessed up to 2 years ] [ Designated as safety issue: No ]
    Date of progression will be defined as the date that the criteria for progressive disease were first met after initiation of dexamethasone. The distribution of event-free survival will be estimated using the method of Kaplan-Meier.


Estimated Enrollment: 103
Study Start Date: January 2012
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ixazomib and dexamethasone)
Patients receive ixazomib 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 or if there is disease progression also receive dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: ixazomib
Given PO
Other Names:
  • MLN9708
  • proteasome inhibitor 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 (ixazomib), used as a single agent in patients with relapsed multiple myeloma, who are proteasome inhibitor naïve (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.

II. To determine the confirmed overall response rate (>=PR) of MLN9708 at a 4 mg dose level in combination with dexamethasone in patients with relapsed multiple myeloma, who are proteasome inhibitor naïve (including bortezomib) naïve 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.

III. To determine the confirmed overall response rate (>=PR) of MLN9708 at a 5.5 mg dose level in combination with dexamethasone in patients with relapsed multiple myeloma, who are proteasome inhibitor naïve (including bortezomib) naïve 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.

III. To determine the overall response rate of MLN9708 at two different doses, in combination with dexamethasone.

IV. To determine the event free survival and overall survival among patients with relapsed myeloma following treatment with MLN9708 at two different doses, in combination with dexamethasone.

OUTLINE:

Patients receive ixazomib 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 or if there is disease progression also receive dexamethasone PO on days 1, 8 and 15. 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
  • Absolute neutrophil count >= 1000/mL
  • Untransfused platelet count >= 75000/mL
  • Hemoglobin >= 8.0 g/dL
  • Total bilirubin =< 1.5 x the upper limit of the normal range (ULN)
  • Aspartate aminotransferase (AST) =< 3 x ULN
  • 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 institution for follow-up during the Active Monitoring Phase of the study; Note: during the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting 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
  • 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
  • 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
  • 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 90 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, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01415882

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Craig B. Reeder         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Vivek Roy         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Shaji K. Kumar         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Shaji Kumar Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01415882     History of Changes
Other Study ID Numbers: MC1181, NCI-2011-02303, 11-001516, MC1181, P30CA015083
Study First Received: August 5, 2011
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

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
BB 1101
Proteasome Inhibitors
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 September 16, 2014