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

NCT03506360 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC1782NCI-2018-0059017-008639
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pembrolizumab works when given together with ixazomib citrate and dexamethasone in treating patients with multiple myeloma that has come back (relapsed). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ixazomib citrate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as 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. Giving pembrolizumab together with ixazomib citrate and dexamethasone may work better in treating patients with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Percentage

  Defined as a partial response or better noted as the objective status on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Up to 9 months

Secondary Outcomes (5)

• >= Very Good Partial Response (VGPR) Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone

  Up to 9 months

• Complete Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone

  Up to 2 years

• Survival Time

  Up to 2 years

• Progression-free Survival

  Up to 2 years

• Incidence of Adverse Events

  Up to 9 months

Other Outcomes (3)

• PDL-1 Expression on Myeloma Cells and Non-tumor Cell Compartments From the Bone Marrow

  Baseline

• Markers of T-cell Activation and Exhaustion

  Baseline up to Cycle 3 (84 days - each Cycle is 28 days)

• Natural Killer Cell Function and Numbers

  Baseline up to Cycle 3 (84 days - each Cycle is 28 days)

Study Arms (1)

Treatment (ixazomib citrate, pembrolizumab, dexamethasone)

EXPERIMENTAL

Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, 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, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (ixazomib citrate, pembrolizumab, dexamethasone)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib citrate, pembrolizumab, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ixazomib citrate, pembrolizumab, dexamethasone)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (ixazomib citrate, pembrolizumab, 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 relapsed, symptomatic multiple myeloma by International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma
• Age \>= 18 years
• Calculated creatinine clearance (using Cockcroft-Gault equation below) \>= 30 mL/min (obtained =\< 14 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 14 days prior to registration)
• Platelet count \>= 75000/mm\^3; Note: Platelet transfusion is not allowed =\< 3 days prior to registration (obtained =\< 14 days prior to registration)
• Hemoglobin \>= 8.0 g/dL (obtained =\< 14 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (obtained =\< 14 days prior to registration)
• Must have relapsed or refractory disease after treatments including three therapies: proteasome inhibitors, immunomodulatory imide drugs (IMiDs), and anti-CD38 antibody
• 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, or 1
• Provide informed written consent

You may not qualify if:

• Myeloma disease that is refractory to ixazomib treatment
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include early stage cancers (carcinoma in situ or stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy
• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• 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, or any ancillary therapy considered investigational =\< 14 days prior to study registration; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Peripheral neuropathy \>= grade 3 on clinical examination or grade 2 with pain during the screening period
• Major surgery =\< 14 days prior to study registration
• Radiotherapy =\< 14 days prior to registration; NOTE: If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of study drugs
• Participation in any other clinical trials with other investigational agents not included in this trial =\< 21 days prior to registration
• Has active autoimmune disease that has required systemic treatment =\< 2 years prior to study registration (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs);
• NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Multiple Myeloma

Interventions

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

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: Yi Lin
• Organization: Mayo Clinic

Lin.Yi@mayo.edu

5072845096

Study Officials

• Yi Lin, M.D., Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 24, 2018
• Study Start: June 19, 2018
• Primary Completion: November 14, 2019
• Study Completion: December 10, 2020
• Last Updated: January 9, 2024
• Results First Posted: November 14, 2022

Record last verified: 2024-01

Locations

US (1)