Carfilzomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in High- Risk SMM

NCT03673826 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: HO1472017-000555-10
• Study Type: interventional
• Target: 58
• Locations: 4 countries
• Sites: 16

Brief Summary

Randomized (2:1) multi-center open-label phase II trial. Patients with high-risk SMM will be enrolled on the study and treated with KRd combination (Cycles 1-9 carfilzomib 20/36 mg/m2, lenalidomide 25 mg, dexamethasone 20 mg cycles 1-4 and 10 mg cycles 5-9) or Rd combination (Cycles 1-9 lenalidomide 25 mg, dexamethasone 20 mg cycles 1-4 and 10 mg cycles 5-9); followed by extended lenalidomide dosing (10 mg days 1-21 of a 28 day cycle for 24 cycles).

Conditions

Smouldering Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate

  Time from study entry to progression or death, whichever comes first

  Until 5 years after randomization or death, whatever comes first

Secondary Outcomes (6)

• MRD status

  9 months

• Progression-free survival-2 (PFS2),

  Until 5 years after randomization or death, whatever comes first

• Duration of response (DOR),

  Until 5 years after randomization or death, whatever comes first

• Overall survival (OS)

  Until 5 years after randomization or death, whatever comes first

• MRD status correlation

  Until 5 years after randomization or death, whatever comes first

Study Arms (2)

Arm A

EXPERIMENTAL

Rd combination (Cycles 1-9 lenalidomide 25 mg, dexamethasone 20 mg cycles 1-4 and 10 mg cycles 5-9); followed by extended lenalidomide dosing (10 mg days 1-21 of a 28 day cycle for 24 cycles).

Drug: Dexamethasone; Drug: Lenalidomide

Arm B

EXPERIMENTAL

KRd combination (Cycles 1-9 carfilzomib 20/36 mg/m2, lenalidomide 25 mg, dexamethasone 20 mg cycles 1-4 and 10 mg cycles 5-9); followed by extended lenalidomide dosing (10 mg days 1-21 of a 28 day cycle for 24 cycles).

Drug: Carfilzomib; Drug: Dexamethasone; Drug: Lenalidomide

Interventions

Carfilzomib DRUG

9 cycles 20/36mg/m2 days 1,2,8,9,15,16

Arm B

Dexamethasone DRUG

4 cycles 20 mg days 1,2,8,9,15,16,22,23 followed by 5 cycles 10mg days 1,2,8,9,15,16,22,23

Arm A; Arm B

Lenalidomide DRUG

9 cycles 25mg days 1-21 followed by 24 extended dosing cycles 10mg days 1-21

Arm A; Arm B

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 based on the 2014 International Myeloma Working Group Criteria(20):
• Serum M-protein ≥3.0 g/dl, or urinary monoclonal protein \>500 mg per 24 hours, and/or monoclonal bone marrow plasma cells ≥10-60 %
• Absence of CRAB symptoms:
• anemia: Hemoglobin \<6.2 mmol/L (10 g/dl) or a hemoglobin value of \>1.2 mmol/L (2 g/dL) below the lower limit of normal
• renal failure: serum creatinine \> 2.0 mg/dL or creatinine clearance \< 40 ml/min
• hypercalcemia: serum calcium \>0·25 mmol/L (\>1 mg/dL) higher than the upper limit of normal or \>2·75 mmol/L (\>11 mg/dL)
• Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT
• Absence of myeloma defining events:
• Involved/uninvolved serum free light chain ratio ≥100 with involved free light-chain concentration ≥10 mg/dl
• Presence of 2 or more focal lesions by MRI (2 of which at least 5 mm)
• Clonal bone marrow plasma cell percentage ≥60%
• Patients must have high risk Smoldering Multiple Myeloma based on the Mayo Clinic and/or the PETHEMA criteria:
• factors of Mayo Clinic criteria:
• Bone marrow plasma cells ≥10 %
• Serum M-protein ≥ 3 g/dl

You may not qualify if:

• Patients with symptomatic multiple myeloma (i.e. having myeloma defining events)
• Amyloid Light-chain (AL) amyloidosis
• Patients who are receiving any other investigational agents.
• Treatment with corticosteroids for other indications is permitted
• Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
• History of allergic reactions attributed to immunomodulatory agents and proteasome inhibitors.
• Uncontrolled hypertension or diabetes
• Pregnant or lactating females.
• Significant cardiovascular disease with NYHA grade III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia
• Active hepatitis B or C infection
• Known or suspected HIV infection
• Incidence of gastrointestinal disease that would prevent absorption.
• Significant neuropathy ≥Grade 3 or grade 2 with pain within 14 days of enrollment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
• History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy during at least 5 years

Sponsors & Collaborators

• Stichting Hemato-Oncologie voor Volwassenen Nederland: lead

Study Sites (16)

CZ-Brno-UHBRNO

Brno, Czechia

Location

CZ-Ostrava-Poruba-FNO

Ostrava, Czechia

Location

IT-Ancona-UMBERTOA

Ancona, Italy

Location

IT-Bologna-MALPHIGI

Bologna, Italy

Location

IT-Brescia-SPEDALICIVILI

Brescia, Italy

Location

IT-Roma-SAPIENZA

Roma, Italy

Location

IT-Torino-MOLINETTE

Torino, Italy

Location

NL-Den Bosch-JBZ

's-Hertogenbosch, Netherlands

Location

NL-Amsterdam-VUMC

Amsterdam, Netherlands

Location

NL-Hoofddorp-SPAARNEGASTHUIS

Hoofddorp, Netherlands

Location

NL-Leeuwarden-MCL

Leeuwarden, Netherlands

Location

NL-Nijmegen-RADBOUDUMC

Nijmegen, Netherlands

Location

NL-Rotterdam-ERASMUSMC

Rotterdam, Netherlands

Location

NL-Sittard-Geleen-ZUYDERLAND

Sittard, Netherlands

Location

NL-Utrecht-UMCUTRECHT

Utrecht, Netherlands

Location

NO-Oslo-OSLOUH

Oslo, Norway

Location

Related Links

• HOVON website

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

carfilzomib; Dexamethasone; Lenalidomide

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; 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

Study Officials

• A. Broijl

  Erasmus MC / HOVON

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 6, 2018
• First Posted: September 17, 2018
• Study Start: November 19, 2018
• Primary Completion: August 1, 2024
• Study Completion (Estimated): December 1, 2028
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (2); NL (8); NO (1); IT (5)