Pembrolizumab, Lenalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma Eligible for Stem Cell Transplant

NCT02880228 | Completed Phase 2 Results DMC

• 3 other identifiers: MC1588NCI-2016-01290P30CA015083
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well pembrolizumab, lenalidomide, and dexamethasone work in treating patients with newly diagnosed multiple myeloma that are eligible for stem cell transplant. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide 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. Giving pembrolizumab, lenalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

Conditions

Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Proportion of Complete Response Plus Very Good Partial Response (VGPR)

  The International Myeloma Working Group response criteria was used to assess response to therapy. The proportion of VGPR response at any time during treatment with pembrolizumab added to lenalidomide and dexamethasone will be estimated by the number of patients achieving a VGPR, CR, or sCR at any time divided by the total number of evaluable patients. A very good partial response (VGPR) is defined as as a demonstration of: * Serum and urine M-component detectable by immunofixation but not on electrophoresis c or * greater than 90% reduction in serum m-component and urine m-component \<100 mg/24 h * If the only measurable disease is FLC, a ≥90% reduction in the difference between involved and involved FLC levels The proportion of successes will be estimated by the number of patients demonstrating a VGPR or better 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 112 days

Secondary Outcomes (4)

• Progression-free Survival

  From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years

• Partial Response (PR)

  Up to 112 days

• Proportion of Successful Stem Cell Collection

  Up to 112 days

• Survival Time

  From time of registration to death due to any cause, assessed up to 3 years

Study Arms (1)

Treatment (lenalidomide, dexamethasone, pembrolizumab)

EXPERIMENTAL

Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO daily on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes on days 1 and 22 of course 1, day 15 of course 2, and day 8 of course 3. Courses 1-3 repeat beyond 3 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo stem cell transplantation after 4 courses of treatment.

Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; 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, 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 (lenalidomide, dexamethasone, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (lenalidomide, dexamethasone, pembrolizumab)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (lenalidomide, dexamethasone, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (lenalidomide, dexamethasone, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Diagnosis and previously untreated active multiple myeloma by International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma
• Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 30 mL/min
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelet count \>= 75000/mm\^3
• Hemoglobin \>= 8.0 g/dL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN
• Prior therapy for the treatment of solitary plasmacytoma is permitted, but \> 7 days should have elapsed from the last day of radiation
• NOTE: Prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate, or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
• 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 written informed consent

You may not qualify if:

• Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
• Prior cytotoxic chemotherapy or corticosteroids for the treatment of multiple myeloma
• NOTE: Prior corticosteroid use for the treatment of non-malignant disorders is permitted
• Diagnosed or treated for another malignancy =\< 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease.
• NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• 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
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Lenalidomide; 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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Shaji K Kumar MD
• Organization: Mayo Clinic

kumar.shaji@mayo.edu

5072842511

Study Officials

• Shaji Kumar

  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: August 18, 2016
• First Posted: August 26, 2016
• Study Start: September 16, 2016
• Primary Completion: July 6, 2017
• Study Completion: July 29, 2018
• Last Updated: July 30, 2019
• Results First Posted: July 17, 2019

Record last verified: 2019-04

Locations

US (2)