The REST (Replacing Steroids in the transplant ineligible) study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Neoplasms [C04]

Trial duration

18 Jun 2021 → ongoing

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510194-34-00

EudraCT number

2020-004425-23

ClinicalTrials.gov

NCT04939844

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To determine how many patients achieve MRD negativity during or after 2 cycles of IVRd, 6 cycles of IVR followed by 10 cycles of IR.

Secondary objectives 5

1. To determine the overall response rate (ORR).
2. To determine the Progression Free Survival (PFS) rate after 2 cycles of IVRd followed by 6 cycles of IVR, 10 cycles of IR and continuous R.
3. To determine the Overall Survival (OS) rate after 2 cycles of IVRd followed by 6 cycles of IVR, 10 cycles of IR and continuous R.
4. To evaluate safety by AEs monitoring and relevant clinical laboratory parameters (hematology and chemistry).
5. To evaluate health-related quality of life (HRQL) and symptoms of steroid toxicity during IVRd (cycle 1 and 2 with dexamethasone) compared to IVR (cycle 4 and 5 without dexamethasone) treatment.

Conditions and MedDRA coding

Multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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: a. Serum monoclonal paraprotein (M-protein) level > 10 g/L or urine M-protein level >200 mg/24 hours; or b. 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 7

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. An 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 5

1. The proportion of patients who achieve PR or better after 2 cycles of IVRd followed by 6 cycles of IVR, followed by 10 cycles of IR.
2. The PFS rate
3. The OS rate
4. The number of AEs and relevant laboratory parameters monitored at every visit (see SoA) from inclusion until end of study.
5. The change in HRQL trajectories and steroid toxicity over time (day 22 – day 1) during IVRd (cycle 1 and 2) compared to IVR (cycle 4 and 5).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Fredrik Schjesvold

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Fredrik Schjesvold

Third parties 1

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications