Idasanutlin, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

NCT02633059 | Completed Phase 1 Results DMC FDA Drug

• 6 other identifiers: MC1582NCI-2015-02155NP29909X16066MMRC-06115-003348
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 8

Brief Summary

This phase I/II trial studies the side effects and best dose of idasanutlin and ixazomib citrate when given together with dexamethasone in treating patients with multiple myeloma that has returned after a period of improvement. Drugs used in chemotherapy, such as idasanutlin and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving idasanutlin, ixazomib citrate, and dexamethasone together may work better in treating patients with multiple myeloma.

Conditions

Loss of Chromosome 17p; Recurrent Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• The Number of Participants Who Experienced Dose Limiting Toxicities. Maximum Tolerated Dose (MTD) of Ixazomib Citrate and Idasanutlin in Combination With Dexamethasone (Phase I)

  Defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). DLT is graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  28 days

• Rate of Confirmed Response, Defined as a Patient Who Has Achieved a Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR) on Two Consecutive Evaluations (Phase II)

  Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

  Up to 6 months

Secondary Outcomes (6)

• Incidence of Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (Phase I)

  30 days after the last dose of study treatment, up to 3 years

• Incidence of Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (Phase II)

  Up to 6 months

• Overall Survival (Phase II)

  Up to 3 years

• Progression Free Survival (Phase II)

  Up to 3 years

• Rate of Complete Response (CR) (Phase II)

  Up to 6 months

Other Outcomes (3)

• Changes in Macrophage Inhibitory Cytokine-1 (MIC) Levels

  Baseline up to 6 months

• Impact of MDM2 Inhibition on Activation of p53 and Clonal Selection

  Up to 6 months

• Potential Biomarkers Associated With Response Determined Using Gene Expression Profiling

  Up to 6 months

Study Arms (1)

Treatment (ixazomib citrate, idasanutlin, dexamethasone)

EXPERIMENTAL

Patients receive ixazomib citrate PO on days 1, 8, and 15 and idasanutlin PO QD on days 1-5 every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive dexamethasone PO on days 1, 8, 15, and 22 every 28 days for 12 courses at the discretion of the treating physician.

Drug: Dexamethasone; Drug: Idasanutlin; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Treatment (ixazomib citrate, idasanutlin, dexamethasone)

Idasanutlin DRUG

Given PO

Also known as: RG-7388, RG7388, RO-5503781, RO5503781

Treatment (ixazomib citrate, idasanutlin, dexamethasone)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib citrate, idasanutlin, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ixazomib citrate, idasanutlin, dexamethasone)

Pharmacological Study OTHER

Correlative studies

Treatment (ixazomib citrate, idasanutlin, dexamethasone)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of multiple myeloma (MM) with deletion 17p (del17p) or monosomy 17 by fluorescence in situ hybridization (FISH) who have received at least one line of therapy
• Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 30 mL/min
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x upper limit of normal (ULN)
• Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN)
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelet count \>= 75,000/mm\^3
• Hemoglobin \>= 8.0 g/dL
• NOTE: white blood count and platelet count criteria must be met without any transfusion or growth factor support
• Patients with measurable disease defined as at least one of the following:
• Serum monoclonal protein \>= 1.0 g/dL by protein electrophoresis
• \> 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 or 2
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only

You may not qualify if:

• Other malignancy requiring active therapy
• EXCEPTIONS: Non-melanoma skin cancer, ductal carcinoma in situ (DCIS) or carcinoma-in-situ of the cervix
• NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
• 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 2 peripheral neuropathy, or grade 1 with pain on clinical examination during the screening period
• Major surgery =\< 14 days before study registration
• All CYP2C8 inhibitors, inducers, and substrates should be discontinued \>= 7 days prior to registration; systemic treatment with CYP2C8 inhibitors (anastrozole, montelukast, quercetin, trimethoprim, gemfibrozil, rosiglitazone, pioglitazone), inducers (carbamazepine, phenytoin, rifabutin, rifampin), or substrates (amiodarone, repaglinide, rosiglitazone, sorafenib, torsemide) should be discontinued \>= 7 days prior to registration
• Systemic treatment with strong inhibitors of CYP3A4 (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, Gingko biloba, St. John's wort) are not allowed =\< 14 days before registration
• 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
• Corrected QT (QTc) \> 470 milliseconds (msec) on a 12-lead ECG obtained during the Screening period
• Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG
• Known human immunodeficiency virus (HIV) positive
• Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (8)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Chromosome 17 deletion; Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; RG7388; ixazomib

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; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Shaji Kumar
• Organization: Mayo Clinic

Kumar.Shaji@mayo.edu

507-284-5096

Study Officials

• Shaji Kumar, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 17, 2015
• Study Start: December 30, 2015
• Primary Completion: January 31, 2021
• Study Completion: November 1, 2022
• Last Updated: September 19, 2024
• Results First Posted: December 2, 2022

Record last verified: 2024-08

Locations

US (8)