A prospective phase II study to assess the minimal residual disease after ixazomib plus lenalidomide plus dexamethasone (IRd) treatment for newly diagnosed transplant eligible patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

HUS-Yhtymae

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

1 Aug 2016 → ongoing

Decision date (initial)

2024-10-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

HUS-Yhtymae

External identifiers

EU CT number

2024-517321-99-00

EudraCT number

2015-004863-35

ClinicalTrials.gov

NCT03376672

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To investigate the protocol treatment efficacy based on serological and bone marrow analyses including minimal residual disease assessment by MFC and safety of IRd induction followed by ASCT, IRd consolidation and IR or R maintenance

Conditions and MedDRA coding

Myeloma multiplex

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Newly diagnosed transplant eligible male or female multiple myeloma patients, 18-70 years of age, who have not received prior treatment for multiple myeloma 2. Symptomatic and measurable disease diagnosed by standard criteria; International Myeloma Working Group, CRAB and SLIM-CRAB (biomarker) criteria 3. Voluntary written informed consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. 4. Female patients who: • Are postmenopausal for at least 1 year before the screening visit, OR • Are surgically sterile, OR • If they are of childbearing potential, fertile, agree to practice 2 effective methods of contraception (see 7.8 Pregnancy; acceptable contraception methods), at the same time, and agree to ongoing pregnancy testing and adhere to the guidelines of the lenalidomide pregnancy prevention program from the time of signing the informed consent form through 90 days after the last dose of study drug, OR Hospital District of Helsinki and Uusimaa/Helsinki University Hospital (HUS) Clinical Study Protocol [IISR-2015-101282-X16085] EudraCT 2015-004863 35 NMSG 23/15 Confidential 43 V8 05Mar2022 • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: • Agree to practice effective barrier contraception and adhere to the guidelines of the lenalidomide pregnancy prevention program during the entire study treatment period and through 90 days after the last dose of study drug, OR • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception. 4. Patients must have a diagnosis of a symptomatic multiple myeloma without any previous therapies except dexamethasone 160 mg dose, or comparable dose of other steroids, and local radiotherapy for symptom control 5. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2. 6. Patients must meet the following clinical laboratory criteria: • Absolute neutrophil count (ANC) ³ 1,000/mm3 (≥ 1.0 x 109/L) and platelet count ³ 75,000/mm3 (75 x 109/L). Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. • Total bilirubin £ 1.5 ´ the upper limit of the normal range (ULN). • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) £ 3 ´ ULN. • Calculated creatinine clearance ³ 30 mL/min (Cockcroft-Gault estimation of creatinine clearance (CRcl): CRcl (mL/min) = (140 - age) (weight [kg]) / 72 (serum creatinine [mg/dL]); for females, multiply by 0.85 (Cockcroft DW. 1976, Luke DR. 1990). 7. Patient must be willing and able to adhere to the study protocol visit schedule and other protocol requirements. 8. Negative pregnancy test at inclusion if applicable Hospital District

Exclusion criteria 1

1. 1. Female patients who are lactating or have a positive serum pregnancy test during the screening period. 2. Major surgery within 14 days before enrollment. 3. Radiotherapy within 14 days before enrollment 4. Central nervous system involvement with multiple myeloma. 5. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. 6. Inability, unwillingness or contraindication to use thrombosis prophylaxis or antithrombotic therapy or herpes zoster prophylaxis 7. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension (blood pressure without medication ≥ 200/120), uncontrolled cardiac arrhythmias (other than fibrillatio atriorum with adequate anticoagulation or superventricular or ventricular extrasystolia, symptomatic congestive heart failure (NYHA classification Appendix 14.7), unstable angina, or myocardial infarction within the past 6 months. 8. Systemic treatment, within 14 days before the first dose of ixazomib, strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort. 9. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 10. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol. 11. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 12. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or lenalidomide including difficulty swallowing. Hospital District of Helsinki and Uusimaa/Helsinki University Hospital (HUS) Clinical Study Protocol [IISR-2015-101282-X16085] EudraCT 2015-004863 35 NMSG 23/15 Confidential 45 V8 05Mar2022 13. Diagnosed or treated for another malignancy within 5 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 14. Patient has Grade 1 polyneuropathy with pain or worse on clinical examination during the screening period. 15. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. 16. Patients that have previously been treated for multiple myeloma or smoldering myeloma with ixazomib or any other therapy, or participated in a study with ixazomib whether treated with ixazomib or not. 17. Primary plasma cell leukemia, POEMS syndrome, Waldenström disease, myelodysplastic syndrome or myeloproliferative disease 18. Systemic AL amyloidosis/primary amyloidosis or myeloma associated amyloidosis. 19. Allogeneic stem cell transplantation planned 20. Participants receiving any other investigational agents or received within 60 days

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To determine the proportion of patients with undetectable flow MRD with sensitivity of 10-5 at any time during protocol treatment.

Investigational products

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

Test 3

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

HUS-Yhtymae

Sponsor organisation

HUS-Yhtymae

Address

Stenbackinkatu 9

City

Helsinki

Postcode

00290

Country

Finland

Scientific contact point

Organisation

HUS-Yhtymae

Contact name

HUS-Yhtymae

Public contact point

Organisation

HUS-Yhtymae

Contact name

HUS-Yhtymae

Sponsor responsibilities

Article 77 compliance

HUS-Yhtymae

Contact point sponsor

HUS-Yhtymae

Article 77 implementation

HUS-Yhtymae

Locations

4 EU/EEA countries · 16 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 18 files

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

Application history

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