MLN9708 and Dexamethasone for High-Risk Smoldering Multiple Myeloma

NCT01660997 | Withdrawn Phase 2

• 2 other identifiers: 12018012-C-0180
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Multiple Myeloma

Keywords

Proteasome Inhibitor; Induction Combination Therapy; Maintenance Strategy; Potent Anti-Myeloma Effect; Precursor Disease

Outcome Measures

Primary Outcomes (1)

• Response rate

  3 years

Secondary Outcomes (2)

• Progression-free survival

  4 years

• Duration of response

  3 years

Interventions

MLN9708 DRUG

Dexamethasone DRUG

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Related Publications (3)

• Perez-Persona E, Vidriales MB, Mateo G, Garcia-Sanz R, Mateos MV, de Coca AG, Galende J, Martin-Nunez G, Alonso JM, de Las Heras N, Hernandez JM, Martin A, Lopez-Berges C, Orfao A, San Miguel JF. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood. 2007 Oct 1;110(7):2586-92. doi: 10.1182/blood-2007-05-088443. Epub 2007 Jun 18.

  PMID: 17576818 BACKGROUND

• Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J, Clark RJ, Melton LJ 3rd, Gertz MA, Kumar SK, Fonseca R, Jelinek DF, Rajkumar SV. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood. 2008 Jan 15;111(2):785-9. doi: 10.1182/blood-2007-08-108357. Epub 2007 Oct 17.

  PMID: 17942755 BACKGROUND

• Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kroger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010 Jun;24(6):1121-7. doi: 10.1038/leu.2010.60. Epub 2010 Apr 22.

  PMID: 20410922 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Carl O Landgren, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 9, 2012
• Study Start: July 30, 2012
• Primary Completion: March 11, 2014
• Study Completion: March 11, 2014
• Last Updated: December 16, 2019

Record last verified: 2014-03-11