A Nationwide Phase 2 Trial of Patients With Smoldering and Active Multiple Myeloma (MM)

NCT03815279 | Enrolling By Invitation Phase 2 DMC

• 1 other identifier: LSH-17-001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the efficacy of treating patients with intermediate risk smoldering multiple myeloma (SMM) with combinational therapy with dexamethasone and lenalidomide (Rd) and patients with high risk SMM with combinational therapy with Rd and carfilzomib.

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Keywords

Multiple Myeloma; Smoldering Multiple Myeloma; Carfilzomib; Lenalidomide; Screening

Outcome Measures

Primary Outcomes (1)

• Rate of MRD negativity

  Minimal residual disease (MRD) as determined VDJ sequencing

  36 months after study enrollment

Secondary Outcomes (2)

• Progression free survival

  Up until 3 years after treatment

• Overall survival

  Up until 3 years after treatment

Study Arms (2)

High-risk SMM and MM

EXPERIMENTAL

Twelve cycles of Carfilzomib-Lenalidomide-Dexamethason. Each cycle is 28 days. Carfilzomib intravenous, days 1, 8 and 15 (starting dose, 20 mg/m2 on day 1 of cycle 1; target dose, 56 mg/m2 thereafter) during cycles 1 through 12. Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks then 20 mg weekly for 16 weeks and thereafter 10 mg weekly for 16 weeks. Maintenance (1 year): Carfilzomib intravenous days 1 and 15 (56 mg/m2) during cycles 13 through 24. Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks Dexamethasone 10 mg weekly for 52 weeks.

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Intermediate-risk SMM

EXPERIMENTAL

Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks, then 20 mg weekly for 16 weeks. Maintenance (1 year): Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks.

Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib will be administered intravenously three times per cycle (28 day cycles) for cycle 1-12. Thereafter twice per cycle for cycle 13-24

Also known as: Kyprolis

High-risk SMM and MM

Lenalidomide DRUG

Lenalidomide PO once daily on days 1-21 of a 28 day cycle

Also known as: Revlimid

High-risk SMM and MM; Intermediate-risk SMM

Dexamethasone DRUG

Dexamethasone will be administered weekly

Also known as: Dexasone

High-risk SMM and MM; Intermediate-risk SMM

Eligibility Criteria

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

You may qualify if:

• Age more than 18 years.
• Active MM or
• Smoldering myeloma, which is untreated, as defined by: Measurable M spike OR pathological FLC ratio AND bone marrow PC% \> 10%
• The following laboratory values obtained ≤ 30 days prior to registration
• Calculated creatinine clearance ≥ 30mL/min (using CKD-EPI equation)
• Absolute neutrophil count (ANC) \> 1000/mm3
• Platelet count \> 75000/mm3
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin ≤ 1.5 x ULN
• ALT and AST ≤ 3 x ULN
• Measurable disease as defined by at least one of the following:
• Serum monoclonal protein \> 1.0g/L
• \> 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
• 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, DHEA, anakinra, pamidronate or zoledronic acid is permitted. Any additional agents not listed must be approved by the Principal Investigator.

You may not qualify if:

• MGUS or low-risk smoldering myeloma.
• Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception (per protocol)
• Other co-morbidity which would interfere with subject'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 within 30 days prior to C1D1.
• Major surgery ≤14 days prior to C1D1.
• Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. Note: Prior to trial entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• Known human immunodeficiency virus (HIV) positive.
• Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
• Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products.
• Known allergies, hypersensitivity, or intolerance to trial drugs.
• Inability to comply with protocol/procedures.

Sponsors & Collaborators

• Landspitali University Hospital: lead
• Amgen: collaborator
• Celgene: collaborator
• University of Iceland: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (1)

Landspitali University Hospital

Reykjavik, 101, Iceland

Location

MeSH Terms

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Interventions

carfilzomib; Lenalidomide; 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; Precancerous Conditions; Hypergammaglobulinemia

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Sigurdur Y Kristinsson, MD, PhD

  Landspitali University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: An investigator initiated, academic, non-randomized, open-label phase 2 study that will assess carfilzomib, lenalidomide and dexamethasone regimen as treatment in patients with intermediate-risk (not carfilzomib) or high-risk SMM or active MM.

Study Record Dates

• First Submitted: January 9, 2019
• First Posted: January 24, 2019
• Study Start: June 24, 2019
• Primary Completion: January 1, 2024
• Study Completion (Estimated): January 1, 2028
• Last Updated: August 16, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

IC (1)