Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM): A nationwide phase 2 trial of patients with smoldering and active multiple myeloma (MM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Landspitali

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2024-12-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519353-11-00

EudraCT number

2017-004785-10

ClinicalTrials.gov

NCT03327597

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

This is a phase II study to assess the efficacy of treating patients with intermediate-risk SMM with combinational therapy with dexamethasone and lenalidomide and treating patients with high risk SMM with combinational therapy with dexamethasone, lenalidomide, and carfilzomib. The primary objective is to determine MRD negativity rate at three years after study enrollment.

Secondary objectives 10

1. To determine the MRD negativity rate at the end of 6 months, 12 months, 24 months and at two years after the completion of treatment.
2. To determine the progression free survival and overall survival.
3. To determine duration of response.
4. To determine rate of adverse events
5. To determine the toxicities associated with this treatment approach in subjects with SMM.
6. To evaluate the incidence of myeloma after population-based treatment of SMM.
7. Various correlative work and relation to clinical outcome.
8. To describe quality of life of patients.
9. To describe the safety of the combination therapy.
10. Exploratory objective to assess the efficacy of treating active MM, identified through screening, with combinational therapy with dexamethasone, lenalidomide, and carfilzomib.

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Active MM or SMM which is untreated
2. At least 18 years of age, with at least 6 months of expected survival
3. Active MM or SMM (defined as measurable M spike OR pathological FLC ratio AND bone marrow PC% > 10%) which is untreated
4. Laboratory values, see protocol
5. Prior therapy for the treatment of solitary plasmacytoma is permitted, but >7 days should have elapsed from the last day of radiation.
6. Measurable disease as defined by at least ONE of the following: Serum monoclonal protein >1.0 g/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
7. ECOG performance status (PS) 0, 1 or 2
8. Provide informed written consent
9. Negative pregnancy test done ≤7 days prior to entry, for women of childbearing potential only
10. Willing to follow strict birth control measures as outlined in the protocol
11. Patients must be willing and able to adhere to the study schedule and other protocol requirement

Exclusion criteria 13

1. MGUS or low risk smoldering myeloma
2. Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease
3. Pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception
4. Other co-morbidity which would interfere with subject's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
5. Other concurrent chemotherapy, or any ancillary therapy considered investigational
6. Peripheral neuropathy > Grade 3 on clinical examination or grade 2 with pain within 30 days prior to C1D1
7. Major surgery ≤14 days prior to C1D1
8. Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
9. Known human immunodeficiency virus (HIV) positive
10. Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
11. Any medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol
12. Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients or known sensitivity to mammalian-derived products
13. Inability to comply with protocol/procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary: Proportion of participants diagnosed with intermediate or high risk SMM that have MRD negativity three year from study enrollment

Secondary endpoints 4

1. Clinical response by IMWG
2. Clinical outcomes by IMWG
3. Safety
4. Correlation with correlative and clinical outcomes

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Landspitali

Sponsor organisation

Landspitali

Address

Skaftahlid 24

City

Reykjavik

Postcode

105

Country

Iceland

Scientific contact point

Organisation

Landspitali

Contact name

Clinical Research Center

Public contact point

Organisation

Landspitali

Contact name

Clinical Research Center

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 5 files

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

Application history

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