Ixazomib (MLN9708) and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study

NCT02697383 | Completed Phase 1

• 1 other identifier: 15-294
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to see what effects, good and/or bad, the combination of ixazomib and dexamethasone has on the patient and the smoldering multiple myeloma.

Conditions

Multiple Myeloma; High Risk Smoldering Multiple Myeloma

Keywords

Ixazomib (MLN9708); Dexamethasone; 15-294

Outcome Measures

Primary Outcomes (1)

• best response

  best overall response rate (PR or better) Stringent Complete Response (sCR) Complete Response as defined below plus: Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence (presence/absence of clonal cells is based on the kappa/ lambda ratio. Complete Response (CR) Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow Very Good Partial Response (VGPR) Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100mg per 24h Partial Response (PR) ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to \<200mg per 24h. If the serum and urine M-protein are unmeasureable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria

  up to 12 cycles of treatment (28 day cycle)

Study Arms (1)

Ixazomib (MLN9708) and Dexamethasone

EXPERIMENTAL

Patients with high risk SMM will be enrolled on the pilot study and treated with 2 drug combination (Cycles 1-12 Ixazomib at 4 mg weekly on days 1, 8 and 15, and dexamethasone on days 1, 8, 15 and 22 of 28 day cycle); the dexamethasone dose will be 40 mg/week the first 4 cycles, thereafter 20 mg/week.

Drug: Ixazomib (MLN9708); Drug: Dexamethasone

Interventions

Ixazomib (MLN9708) DRUG

Ixazomib (MLN9708) and Dexamethasone

Dexamethasone DRUG

Ixazomib (MLN9708) and Dexamethasone

Eligibility Criteria

• Age: 18 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 Department of Pathology, based on the International Myeloma Working Group Criteria
• Serum M-protein ≥3 g/dl and/or bone marrow plasma cells ≥10 %,
• Absence of anemia attributed to the plasma cell disorder\*: Hemoglobin \>10 g/dl or not more than 2g/dL below the lower limit of normal
• Absence of renal failure attributed to the plasma cell disorder\*: calculated creatinine clearance (according to Cockcroft-Gault method, MDRD, or CKD-EPI formulae) \> 30 mL/min (or alternatively based on standard creatinine level criteria of 2 mg/dl)
• Absence of hypercalcemia attributed to the plasma cell disorder\* (: Ca \< 10.5 mg/dl or ≤ 2.5 mmol/L
• Absence of lytic bone lesion
• Absence of Clonal bone marrow plasma cell percentage ≥60%
• Absence of Involved: uninvolved serum free light chain ratio ≥100
• Absence \>1 focal lesions on MRI studies
• \* To be determined based on clinical and laboratory assessment by the primary oncologist
• "High-risk SMM" per Mayo Clinic or Spanish PETHEMA criteria
• Measurable disease within the past 4 weeks defined by any one of the following
• Serum monoclonal protein ≥ 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)

You may not qualify if:

• Participation in other clinical trials, including those with other investigational agents not included in this trial and throughout the duration of this trial; within at least 5 half-lives of previous therapy for smoldering myeloma at start of this trial.
• Prior therapy for SMM with a proteasome inhibitor.
• Patients with a diagnosis of MM per standard IMWG criteria
• 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.
• Females patients who are lactating or have a positive serum pregnancy test during the screening period.
• Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
• Patient has ≥ Grade 1 peripheral neuropathy with pain on clinical examination during the screening period.
• 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

• Memorial Sloan Kettering Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (6)

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, 10065, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

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

• Sham Mailankody, MBBS

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 3, 2016
• Study Start: February 1, 2016
• Primary Completion: May 8, 2024
• Study Completion: May 8, 2024
• Last Updated: May 13, 2024

Record last verified: 2024-05

Locations

US (6)