A study comparing treatment with Daratumumab, Velcade (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) to standard treatment (VRd) in patients with previously untreated multiple myeloma who are eligible for high-dose therapy

Australia, Belgium, Czechia, Denmark, France, Greece, Italy, Netherlands, Norway, Poland, Spain, Switzerland, Turkey (ICTRP)

ICTRP Trial ID
NCT03710603 (ICTRP)

Official title (approved by ethics committee)
A Phase 3 Study Comparing Daratumumab, Velcade (bortezomib), Lenalidomide, and Dexamethasone (D-VRd) vs Velcade, Lenalidomide, and Dexamethasone (VRd) in Subjects with Previously Untreated Multiple Myeloma who are Eligible for High-Dose Therapy (BASEC)

Academic title
A Phase 3 Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) vs VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects With Previously Untreated Multiple Myeloma Who Are Eligible for High-dose Therapy (ICTRP)

Public title
Daratumumab, VELCADE (Bortezomib), Lenalidomide and Dexamethasone Compared to VELCADE, Lenalidomide and Dexamethasone in Subjects With Previously Untreated Multiple Myeloma (ICTRP)

Disease under investigation
Multiple Myeloma (ICTRP)

Intervention under investigation
Drug: Daratumumab;Drug: Velcade;Drug: Lenalidomide;Drug: dexamethasone (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
Gender: All
Maximum age: 70 Years
Minimum age: 18 Years
Inclusion Criteria:

1.18 to 70 years of age, inclusive.

2.Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven
plasmacytoma and documented multiple myeloma satisfying at least one of the calcium,
renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:

CRAB criteria:

1. Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than upper limit of
normal (ULN) or >2.75 mmol/L (>11 mg/dL)

2. Renal insufficiency: creatinine clearance <40 mL/min or serum creatinine >177 ?mol/L
(>2 mg/dL)

3. Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin <10 g/dL

4. Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or
Positron-emission tomography (PET)-CT

Biomarkers of Malignancy:

a. Clonal bone marrow plasma cell percentage =60% b. Involved: uninvolved serum free
light chain (FLC) ratio =100 c. >1 focal lesion on magnetic resonance imaging (MRI)
studies

3.Measurable disease as defined by any of the following:

1. Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level
=200 mg/24 hours; or

2. Light chain multiple myeloma without measurable disease in the serum or the urine:
Serum immunoglobulin FLC =10 mg/dL and abnormal serum immunoglobulin kappa lambda
FLC ratio

4.Newly diagnosed subjects for whom high-dose therapy and autologous stem cell
transplantation (ASCT) is part of the intended treatment plan.

5.Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

6.Clinical laboratory values meeting the following criteria during the Screening
Phase (Screening hematology and chemistry tests should be repeated if done more than
3 days before C1D1):

Adequate bone marrow function:

1. Hemoglobin =7.5 g/dL (=4.65 mmol/L; prior red blood cell (RBC) transfusion or
recombinant human erythropoietin use is permitted however transfusions are not
permitted within 7 days of randomization to achieve this minimum hemoglobin count);

2. Absolute neutrophil count (ANC) =1.0 x 109/L (granulocyte-colony stimulating factor
(G-CSF) use is permitted);

3. Platelet count =50 x 109/L if bone marrow is >50% involved in myeloma. Otherwise =75
x 109/L

Adequate liver function:

1. Aspartate aminotransferase (AST) =2.5 x ULN;

2. Alanine aminotransferase (ALT) =2.5 x ULN;

3. Total bilirubin =1.5 x ULN (except in subjects with congenital bilirubinemia, such
as Gilbert syndrome, direct bilirubin =1.5 x ULN)

Adequate renal function:

1. Estimated creatinine clearance =30 mL/min. Creatinine clearance may be calculated
using Cockcroft-Gault, estimated Glomerular filtration rate (eGFR) (Modified Diet in
Renal Disease (MDRD)), or Chronic Kidney Disease (CKD)-epi formula

2. Corrected serum calcium =13.5 mg/dL (=3.4 mmol/L); or free ionized calcium =6.5
mg/dL (=1.6 mmol/L)

7. Female subjects of reproductive childbearing potential must commit to either
abstain continuously from heterosexual sexual intercourse or to use 2 methods
of reliable birth control simultaneously during the Treatment Period, during
any dose interruptions, and for 3 months after the last dose of any component
of the treatment regimen. Sexual abstinence is considered a highly effective
method only if defined as refraining from heterosexual intercourse during the
entire period of risk associated with the study drug. This birth control method
must include one highly effective form of contraception (tubal ligation,
intrauterine device (IUD), hormonal [birth control pills, injections, hormonal
patches, vaginal rings or implants] or partner's vasectomy) and one additional
effective contraceptive method (male latex or synthetic condom, diaphragm, or
cervical cap). Contraception must begin 4 weeks prior to dosing. Reliable
contraception is indicated even where there has been a history of infertility,
unless due to hysterectomy or bilateral oophorectomy.

8. A woman of childbearing potential must have 2 negative serum or urine pregnancy
tests at Screening, first within 10 to 14 days prior to dosing and the second
within 24 hours prior to dosing.

9. A woman must agree not to donate eggs (ova, oocytes) for the purposes of
assisted reproduction during the study and for a period of 3 months after
receiving the last dose of any component of the treatment regimen.

10. Male subjects of reproductive potential who are sexually active with females of
reproductive potential must always use a latex or synthetic condom during the
study and for 3 months after discontinuing study treatment (even after a
successful vasectomy).

11. Male subjects of reproductive potential must not donate sperm during the study
or for 3 months after the last dose of study treatment.

12. Signed an informed consent form (ICF) (or their legally acceptable
representative must sign) indicating that he or she understands the purpose of,
and procedures required for, the study and is willing to participate in the
study.

13. Able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

1. Prior or current systemic therapy or stem cell transplant (SCT) for any plasma cell
dyscrasia, 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. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the
National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Version 5.

3. Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years
of date of randomization (exceptions are adequately treated basal cell or squamous
cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other
non-invasive lesion that in the opinion of the investigator, with concurrence with
the sponsor's medical monitor, is considered cured with minimal risk of recurrence
within 3 years).

4. Radiation therapy within 14 days of randomization.

5. Plasmapheresis within 28 days of randomization.

6. Clinical signs of meningeal involvement of multiple myeloma.

7. Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1
second (FEV1) <50% of predicted normal (for subjects =65 years old FEV1 <50% or
diffusing capacity of the lungs for carbon monoxide [DLCO] <50%)

8. Moderate or severe persistent asthma within the past 2 years, or currently has
uncontrolled asthma of any classification. (Note that subjects who currently have
controlled intermittent asthma or controlled mild persistent asthma are allowed in
the study).

9. Any of the following:

1. Seropositive for human immunodeficiency virus (HIV)

2. Seropositive for hepatitis B (defined by a positive test for hepatitis B
surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who
are positive for antibodies to hepatitis B core antigen (ICTRP)

not available

Primary and secondary end points
Progression Free Survival (PFS) (ICTRP)

Overall MRD Negativity Rate;Percentage of Participants With Overall Response Rate (ORR);Percentage of Participants With Overall Complete Response (CR) or Better;Progression-free Survival on the Next Line of Therapy (PFS2);Overall Survival (OS);Time to Response;Duration of Response;Pharmacokinetic Concentrations of Daratumumab;Determine the Incidence of Anti-daratumumab Antibodies (Immunogenicity) for All Subjects Who Receive at Least 1 Dose of Daratumumab and Determine the Incidence of Anti-rHuPH20 Antibodies;Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) Score and the Difference Between-treatment Arms;Change in EORTC QLQ- 20-item Multiple Myeloma Module (MY-20) Score and the Difference Between-treatment Arms;EQ-5D-5L Health Utility Values and the Difference Between-treatment Arms;Stem Cell Yield After Mobilization;Time to Engraftment Post-ASCT (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
Janssen Research & Development, LLC (ICTRP)

Additional contacts
not available

Secondary trial IDs
EMN17/54767414MMY3014 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT03710603 (ICTRP)