REST - Replacing Steroids in the Transplant Ineligble

Multiple Myeloma Clinical Trial

— REST  

Official title:

Isatuximab in Combination With Bortezomib and Lenalidomide With Minimal Dexamethasone in Transplant-ineligible Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04939844
• Other study ID #: OMC02/20
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 29, 2021
• Est. completion date: October 2026

Study information

• Verified date: February 2023
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Approximately 53 participants will be screened to achieve 50 enrolled (sample size) to study intervention.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.Bone marrow MRD Euroflow NGF will be assessed once in participants achieving CR/sCR during the first 18 cycles of treatment, and in all participants (except for those who already are defined as MRD negative) achieving VGPR or better after finishing the first 18 cycles of treatment to assess. Those who are in VGPR and are MRD negative after 18 cycles of treatment will be response evaluated monthly for up to 4 months and if they become >CR during this period they are defined as MRD negative. The cut-off for MRD negativity is 100 plasma cells per 100 million nucleated cells (10-5).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 51
• Est. completion date: October 2026
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Voluntary written informed consent.

2. Participant must be >18 years of age at the time of signing the informed consent.

3. Newly diagnosed multiple myeloma (IMWG criteria) in-eligible for high-dose therapy and ASCT.

4. Measurable disease as defined by the International Myeloma Working Group:

1. Serum monoclonal paraprotein (M-protein) level > 10 g/L or urine M-protein level >200 mg/24 hours; or

2. 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.

5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. ECOG 3 can only be enrolled if caused by myeloma.

6. 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

7. Patient must be willing and able to adhere to the study protocol visit schedule and other protocol requirements.

8. Females of childbearing potential (FCBPs) must have a confirmed negative serum or urine pregnancy test within 10-14 days prior to and again within 24 hours prior to starting study medication.

9. FCBPs and male subjects who are sexually active with FCBP must agree to use highly effective concomitant methods of contraceptive during the intervention period, for at least 5 months after last dose of isatuximab treatment and at least 28 days after last lenalidomide treatment. Male subjects must refrain from donating sperm during this period.

Exclusion Criteria:

1. 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.

2. 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).

3. Active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positivity.

4. 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.

5. No active malignancy with a lower life expectancy than myeloma.

6. Female patients who are lactating or have a positive serum pregnancy test during the screening period.

7. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Isatuximab, bortezomib, lenalidomide, dexamethason
All participants will receive the same treatment as described under arm.

Locations

Country	Name	City	State
Denmark	Zealand University Hospital	Roskilde
Norway	Oslo University Hospital	Oslo
Norway	Helse Stavanger HF	Stavanger
Norway	St. Olav University Hospital	Trondheim

Sponsors (4)

Lead Sponsor	Collaborator
Oslo University Hospital	Helse Stavanger HF, Nordic Myeloma Study Group, St. Olavs Hospital

Countries where clinical trial is conducted

Denmark,  Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall response rate	The proportion of patients who achieve partial response (PR) or better following 18 cycles of study treatment	30 months
Secondary	Progression free survival	The PFS rate of patients receiving 2 cycles of IVRd followed by 6 cycles of IVR, 10 cycles of IR and continuous R	4 years
Secondary	Overall survival	The OS rate of patients receiving 2 cycles of IVRd followed by 6 cycles of IVR, 10 cycles of IR and continuous R.	5 years