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MLN9708 and Dexamethasone for High-Risk Smoldering Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01660997
Recruitment Status : Withdrawn
First Posted : August 9, 2012
Last Update Posted : December 16, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Study Description
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Brief Summary:

Background:

- Smoldering multiple myeloma (SMM) is a condition that can lead to multiple myeloma, a type of blood cancer. In many high-risk cases, SMM can develop into multiple myeloma in less than 2 years. The current standard of care for SMM is follow-up without treatment until multiple myeloma develops. However, some drugs are being studied to see if they can slow down or prevent the disease from progressing. One such drug is MLN9708. It has shown some results against multiple myeloma. Researchers want to combine MLN9708 with dexamethasone to see how it works against high-risk SMM.

Objectives:

- To see if MLN9708 with dexamethasone is a safe and effective treatment for high-risk smoldering multiple myeloma.

Eligibility:

- Individuals at least 18 years of age who have high-risk smoldering multiple myeloma.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and a bone marrow biopsy may also be performed.
  • Participants will take MLN9708 and dexamethasone on a regular schedule for 28 days. They will take each drug four times at regular intervals during each cycle of treatment.
  • Treatment will be monitored with frequent blood tests and imaging studies.
  • Participants will have 12 cycles of treatment. After four cycles, patients will be recommended to have their own stem cells collected and stored. This will allow the potential application of a highdose melpahalan/autologous stem cell transplant in the event there is a need in the future (not part of this study).
  • After 12 cycles, participants will keep taking MLN9708 as long as the disease does not progress and the side effects are not too severe.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: MLN9708 Drug: Dexamethasone Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MLN9708 and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study
Study Start Date : July 30, 2012
Actual Primary Completion Date : March 11, 2014
Actual Study Completion Date : March 11, 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Outcome Measures
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Primary Outcome Measures :
  1. Response rate [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 4 years ]
  2. Duration of response [ Time Frame: 3 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

  • Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma confirmed by the Laboratory of Pathology, NCI based on the International Myeloma Working Group Criteria:

    • Serum M-protein greater than or equal to 3 g/dl and/or bone marrow plasma cells greater than or equal to 10 %,
    • Absence of anemia: Hemoglobin >10 g/dl
    • Absence of renal failure: calculated creatinine clearance (according to MDRD) > 80 ml/min (or alternatively based on standard creatinine level criteria of 2 mg/dl)
    • Absence of hypercalcemia: Ca < 10.5 mg/dl or less than or equal to 2.5 mmol/L
    • Absence of lytic bone lesion
  • High-risk SMM per Mayo Clinic2 or Spanish PETHEMA1 criteria

  • Measurable disease within the past 4 weeks defined by any one of the following:

    • Serum monoclonal protein greater than or equal to 1.0 g/dl
    • Urine monoclonal protein >200 mg/24 hour
    • Serum immunoglobulin free light chain >10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)
  • Age >18 years.
  • ECOG performance status <2.
  • Ability to give informed consent.

  • Patients must have normal organ and marrow function as defined below:

    • absolute neutrophil count >1.0 K/uL
    • Platelets >75 K/uL (Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.)
    • hemoglobin > 8 g/dL(transfusions are permissible)
    • total bilirubin <1.5 X institutional upper limit of normal
    • AST(SGOT)/ALT(SGPT) < 3.0 X institutional upper limit of normal

  • 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 through 30 days after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse.

      • The 2 methods of reliable contraception must include 1 highly effective method and 1 additional effective (barrier) method. Females of childbearing potential must be referred to a qualified provider of contraceptive methods if needed. The following are examples of highly effective and additional effective methods of contraception:

  • Highly effective methods:

    • Intrauterine device (IUD)
    • Hormonal (birth control pills, injections, implants)
    • Tubal Ligation
    • Partner's Vasectomy

Additional effective methods:

  • Male condom
  • Diaphragm

  • Cervical Cap

    -Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:

  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse.

EXCLUSION CRITERIA:

  • Patients who are receiving any other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial.
  • Prior therapy for SMM with a proteasome inhibitor.
  • Patients with a diagnosis of MM.
  • Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy.
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  • Uncontrolled hypertension or diabetes.
  • Pregnant or lactating females.
  • Has refractory GI disease with refractory nausea/vomiting, inflammatory bowel disease, or bowel resection that would prevent absorption.
  • Patient has greater than or equal to Grade 2 peripheral neuropathy.
  • 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.
  • Systemic treatment, within 14 days before study enrollment, 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.
  • Ongoing or active systemic infection, known human immunodeficiency virus (HIV) positive, known active hepatitis B virus hepatitis, or known active hepatitis C virus hepatitis.
  • Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  • Psychiatric illness/social situation that would limit compliance with study requirements.
  • QTc > 470 milliseconds (msec) on a 12-lead EKG obtained during the Screening period. If a machine reading is above this value, the EKG should be reviewed by a qualified reader and confirmed on a subsequent EKG.
  • 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.
  • Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements or GI procedure that could interfere with the oral absorption or tolerance of treatment.
  • Major surgery within 1 month prior to enrollment.
  • Radiotherapy within 14 days before enrollment.
  • Central nervous system involvement (based on clinical assessment).
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
  • No current bisphosphonate therapy (However, prior bisphosphonates or once a year intravenous bisphosphonate for osteoporosis is allowed).
  • Patients with Paget s disease of the bone
  • Recruitment Strategies
  • Patients from the SMM and MGUS Natural History Study (NCI Protocol: 10-C-0096) will be potential candidates.
  • Other participant sources will be from outside physician referrals.
  • Our ongoing natural history study and outside physician referral network have a high representation of minorities.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01660997


Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Carl O Landgren, M.D. National Cancer Institute (NCI)
More Information
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Publications:

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01660997    
Other Study ID Numbers: 120180
12-C-0180
First Posted: August 9, 2012    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: March 11, 2014
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Proteasome Inhibitor
Induction Combination Therapy
Maintenance Strategy
Potent Anti-Myeloma Effect
Precursor Disease
Additional relevant MeSH terms:
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Multiple Myeloma
Smoldering 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
 Precancerous Conditions
Hypergammaglobulinemia
Dexamethasone
Ixazomib
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents