Research study to comparison the effectivenes of combination of drugs called lenalidomide, carfilzomib, dexamethasone with combination of drugs called lenalidomide, bortezomib, dexamethasone, given to patients with newly diagnosed multiple myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Polish Myeloma Consortium

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Nov 2019 → ongoing

Decision date (initial)

2024-12-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Celgene Switzerland Holdings Sàrl · University of Chicago

External identifiers

EU CT number

2024-518473-34-00

EudraCT number

2018-004031-68

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Dose response, Efficacy, Therapy

To compare the MRD-negative complete response status at 12 months after randomization and PFS

Secondary objectives 7

1. To compare the status of MRD-negative disease at 8 and 24 months after randomization between the KRd and VRd arms.
2. To evaluate the duration of MRD-negative status between the two arms
3. To compare the MRD-negative complete response status as best response between two arms.
4. To evaluate the efficacy (rate – ORR - and sustainability -DOR - of PR, VGPR, CR, and sCR) across entire treatment in high risk and low risk patients and as best response of KRd vs. VRd after randomization
5. To determine rates of improvement of the depth of response by at least one category according to IMWG response criteria.
6. To compare overall survival
7. To evaluate the safety and tolerability of KRd compared to VRd

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy per IMWG criteria: • Patients must have received no prior chemotherapy for this disease; • patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis); • prior steroid treatment is allowed provided treatment was not more than 2 weeks in duration and ≤ 160 mg dexamethasone; • patients must not have received any prior treatment with bortezomib or lenalidomide
2. Both transplant and non-transplant candidates are eligible. Transplant candidates must agree at time of consent to defer transplant to the end of study treatment. If patient proceeds to transplant, they will come off study.
3. Diagnosis of symptomatic multiple myeloma as per current IMWG uniform criteria prior to initial treatment
4. Monoclonal plasma cells in the BM 10% or presence of a biopsy-proven plasmacytoma
5. Measurable disease, prior to initial treatment as indicated by one or more of the following: • Serum M-protein ≥ 1 g/dL • Urine M-protein ≥ 200 mg/24 hours • Involved serum free light chains ≥ 10 mg/dL provided that free light chain ratio is abnormal • If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
6. Bone marrow specimen will be required at study entry; available DNA sample from pre-treatment BM will be used for calibration step for MRD evaluation by gene sequencing.
7. Males and females ≥ 18 years of age
8. ECOG performance status of 0-2
9. Adequate hepatic function, with bilirubin ≤ 1.5 x ULN and aspirate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 xULN
10. ANC ≥ 1.0 x 109/L, hemoglobin ≥ 8 g/dL, platelet count ≥ 75 x 109/L.
11. Calculated creatinine clearance (by Cockroft-Gault) ≥ 50 mL/min or serum creatinine below 2 g/dL
12. Female of child bearing potential (FCBP) must have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to initiating lenalidomide. The first pregnancy test must be performed within 10-14 days before and the second pregnancy test must be performed within 24 hours before lenalidomide is prescribed for Cycle 1 (prescriptions must be filled within 7 days).
13. FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study; and 3) for at least 30 days after discontinuation from the study.
14. Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 90 days following discontinuation from the study even if he has undergone a successful vasectomy.
15. All study participants in the US and EU countries (excluding Poland) must be consented to and registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of Revlimid REMS®.
16. Subjects must comply with pregnancy prevention and counseling
17. Voluntary written informed consent.

Exclusion criteria 25

1. Frail, non-transplant candidates, per modified IMWG frailty score (age not counted as a scoring factor)
2. Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as <1.0 g/dL M-protein in serum, <200 mg/24 hr urine M-protein and and FLC <10mg/dL as per IMWG measured by Freelite.
3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
4. Amyloidosis
5. Plasma cell leukemia
6. Waldenström’s macroglobulinemia or IgM myeloma
7. Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
8. Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater
9. Patients not able to tolerate bortezomib, carfilzomib, lenalidomide or dexamethasone
10. Peripheral neuropathy ≥ Grade 2 at screening
11. Diarrhea > Grade 1 in the absence of antidiarrheals
12. CNS involvement
13. Patients who cannot undergo or unwilling to take thromboprophylaxis
14. Uncontrolled or symptomatic angina, arrhythmia, hypertension, CHF, EF< 40%, within 6 months prior to first dose.
15. Pregnant or lactating females
16. Major surgery within 3 weeks prior to first dose.
17. Myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
18. Pulmonary embolism within 6 months prior to first dose.
19. Known moderate or severe persistent asthma or known chronic obstructive pulmonary disease (COPD)
20. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening
21. Uncontrolled diabetes
22. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
23. Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine or are asymptomatic chronic carriers of HBV are eligible.
24. Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
25. Any clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The MRD-negative complete response status at 12 months by NGS and PFS defined as the time to progressive disease or death as defined by IMWG criteria

Secondary endpoints 7

1. The MRD-negative status in each study arm at 8and 24 months
2. Duration of MRD-negative status.
3. MRD-negative complete response
4. Comparing rate of PR or better, VGPR or better, CR or better, or sCR at 8, 12, 24, 36, 48, and 60 months and as best response between the two arms
5. Determine rates of improvement of the depth of response by at least one category according to IMWG response criteria. (For example, an improvement from very good partial response (VGPR) to near complete response (nCR) or better than nCR including conversion from CR to MRD negative disease [overall response]) at specified landmark timepoints.
6. To compare overall survival.
7. Safety and tolerability of KRd vs. VRd

Investigational products

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

Test 13

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Polish Myeloma Consortium

Sponsor organisation

Polish Myeloma Consortium

Address

Ul. Augustyna Szamarzewskiego 84

City

Poznan

Postcode

60-569

Country

Poland

Scientific contact point

Organisation

Polish Myeloma Consortium

Contact name

Dominik Dytfeld

Public contact point

Organisation

Polish Myeloma Consortium

Contact name

Clinical Trial Information Desk

Third parties 2

Locations

3 EU/EEA countries · 11 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 16 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