REST - Replacing Steroids in the Transplant Ineligble

NCT04939844 | Completed Phase 2

• 1 other identifier: OMC02/20
• Study Type: interventional
• Target: 51
• Locations: 2 countries
• Sites: 4

Brief Summary

Newly diagnosed multiple myeloma patients ineligible for HD-ASCT will be included in the study. All participants will receive isatuximab in combination with bortezomib, lenalidomide and minimal dexamethasone until disease progression. The primary objective of this study is the MRD negativity rate during and/or after first 18 cycles of study treatment.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• MRD negativity

  The proportion of patients who achieve MRD negativity measured by NGF Euroflow during and/or after 18 cycles of study treatment.

  34 months

Secondary Outcomes (3)

• Overall response rate

  30 months

• Progression free survival

  4 years

• Overall survival

  5 years

Study Arms (1)

NDMM ineligible for transplant

EXPERIMENTAL

All participants will receive isatuximab in combination with bortezomib, lenalidomide and dexamethasone for 2 cycles, followed by isatuximab in combination with bortezomib and lenalidomide for 6 cycles, followed by isatuximab in combination with lenalidomide for 10 cycles, followed by continuous lenalidomide until disease progression. The cycle duration is 28 days. * Isatuximab will be administered IV at a dose of 10 mg/kg * on D1, D8, D15 and D22 during Cycle 1 * on D1 and D15 during Cycles 2-18 * Bortezomib will be administered SC at a dose of 1,3mg/m2 -on D1, D8 and D15 during Cycles 1-8 * Lenalidomide will be administered PO at a dose of 25mg/day (15 mg/day in participants with GFR \<30mL/minute/1.73m2) -on D1 to D21 during all Cycles. * Dexamethasone will be administered PO at a dose of 20 mg -on D1, D8, D15 and D22 during Cycles 1 and 2

Drug: Isatuximab, bortezomib, lenalidomide, dexamethason

Interventions

Isatuximab, bortezomib, lenalidomide, dexamethason DRUG

All participants will receive the same treatment as described under arm.

NDMM ineligible for transplant

Eligibility Criteria

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

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Voluntary written informed consent.
• Participant must be \>18 years of age at the time of signing the informed consent.
• Newly diagnosed multiple myeloma (IMWG criteria) in-eligible for high-dose therapy and ASCT.
• Measurable disease as defined by the International Myeloma Working Group:
• Serum monoclonal paraprotein (M-protein) level \> 10 g/L or urine M-protein level \>200 mg/24 hours; or
• Light chain multiple myeloma without measurable disease in the serum or the urine: Involved serum immunoglobulin FLC \> 100 mg/L and abnormal serum immunoglobulin kappa lambda FLC ratio.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. ECOG 3 can only be enrolled if caused by myeloma.
• Clinical laboratory values meeting the following criteria during the Screening Phase:
• a. Adequate bone marrow function:
• Hemoglobin \>7,5 g/dL (transfusion is permitted, recombinant human EPO use is permitted, however transfusion is not permitted within 3 days before screening)
• Absolute neutrophil count \> 1.0 x 109/L (G-CSF use is permitted)
• Platelet count \>70 x 109/L
• a) Adequate renal function:
• eGFR\>30 mL/min/m2

You may not qualify if:

• Prior or current systemic therapy for multiple myeloma with the exception of emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
• Radiation therapy for treatment of plasmacytoma(s) within 14 days before treatment (local radiation for pain control or to prevent fracture is allowed within 14 days before treatment).
• Active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positivity.
• Any other serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• No active malignancy with a lower life expectancy than myeloma.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Nordic Myeloma Study Group: collaborator
• St. Olavs Hospital: collaborator
• Helse Stavanger HF: collaborator

Study Sites (4)

Zealand University Hospital

Roskilde, 4000, Denmark

Location

Oslo University Hospital

Oslo, Norway

Location

Helse Stavanger HF

Stavanger, Norway

Location

St. Olav University Hospital

Trondheim, Norway

Location

Related Publications (1)

• Askeland FB, Haukas E, Slordahl TS, Klostergaard A, Alexandersen T, Lysen A, Abdollahi P, Nielsen LK, Hermansen E, Schjesvold F. Isatuximab, bortezomib, lenalidomide, and limited dexamethasone in patients with transplant-ineligible multiple myeloma (REST): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2025 Feb;12(2):e120-e127. doi: 10.1016/S2352-3026(24)00347-8.

  PMID: 39909655 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; Bortezomib; Lenalidomide

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Fredrik H Schjesvold, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Oslo Myeloma Center.

Model Details: This is a Phase 2, investigator initiated, single arm, open-label, multicenter study of isatuximab in combination with bortezomib and lenalidomide (IVR) with minimal dexamethasone, in patients with newly diagnosed multiple myeloma (NDMM) in-eligible for high dose melphalan with autologous stem cell support (HD-ASCT).

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: June 25, 2021
• Study Start: June 29, 2021
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); NO (3)