Multiple Myeloma
Conditions
Keywords
Hematologic Diseases, Neoplasms, Multiple Myeloma, Isatuximab, Cyclophosphamide, Dexamethasone, Bortezomib, Lenalidomide
Brief summary
This is a phase II multi-center, open label, single arm study to evaluate the safety and efficacy of Isatuximab administered intravenously in combination with CyBorD induction treatment and Lenalidomide maintenance treatment in a 28-day long cycle in autologous stem cell transplant-eligible patients.
Detailed description
This is a phase II, multicenter, open label, single arm study that will evaluate the safety and efficacy of Isatuximab administered intravenously at 10 mg/kg in combination with CyBorD induction treatment and Lenalidomide maintenance treatment in a 28-day long cycle in autologous stem cell transplant-eligible patients. The induction treatment consists of four cycles of Isa-CyBorD. Isatuximab will be given on days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of cycle 2-4 in combination with Cyclophosphamide at 300 mg/m2 on days 1, 8, 15 and 22, Bortezomib at 1.5 mg/m2 on days 1, 8, 15 and 22 and Dexamethasone at 40 mg on days 1, 8, 15 and 22 of each 28-day cycle. Following the induction phase, all subjects achieving at least stable disease will have stem cell mobilization per standard institutional procedures. This is followed by high dose chemotherapy (Melphalan 200 mg/m2) and autologous stem cell transplantation. ((If, for unexpected logistical reason, there is a foreseen delay of stem cell mobilization or transplantation of more than eight weeks after the end of cycle four of induction, an additional cycle of Isa-CyBorD can be given at the investigator's discretion.)) The maintenance treatment consisting of Isatuximab at 10 mg/kg administered intravenously on days 1, 8, 15 and 22 of cycle 1, days 1 and 15 of cycle 2 and 3 and day 1 all subsequent 28-day maintenance cycles in combination with Lenalidomide administered orally at 10 mg on days 1-21 of each 28-day cycle will be administered starting at day 100 (+/- 7 days) after the transplant. Lenalidomide, if tolerated well, will be increased to 15 mg starting with cycle 3.
Interventions
OTHERIsatuximab
Brand name for interventional drug is Sarclisa
Sponsors
Canadian Myeloma Research Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study: 1. Males or females, age 18 to 75 years of age. 2. ECOG performance status score of 0, 1 or 2. 3. Life expectancy of at least 9 months 4. Measurable disease according to the IMWG criteria defined as 1. Serum monoclonal paraprotein (M-protein) ≥ 10 g/L (if IgG) or ≥5g/L (if IgA, D, E or M) 2. Urine M-protein ≥ 200 mg/24 h 3. Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/L and an abnormal serum free light chain ratio (\< 0.26 or \> 1 .65) if no M-protein detected in serum or urine 5. Newly Diagnosed Symptomatic Multiple Myeloma by IMWG criteria 6. The following laboratory results must be met within 10 days of first study drug administration: 1. ANC ≥ 1.0 x 109/L 2. Hemoglobin ≥ 80 g/L (transfusions permitted) 3. Platelets ≥ 70 x 109/L (or ≥50 x 109/L if ≥50% plasmacytosis in bone marrow. 4. Calculated CrCl ≥ 30 mL/min 5. AST and ALT ≤ 3.0 x ULN 6. Total bilirubin ≤ 2 x ULN unless known to have Gilbert's disease 7. Corrected serum calcium ≤ 3.5 mmol/L 7. Have signed the informed consent documents indicating that the subject understands the purpose of and procedures required for the study and is willing to participate and adhere to the study protocol. 8. Females with child-bearing potential (FCBP) must agree to use 2 reliable forms of contraception\* simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including during dose interruptions), and for at least 150 days after study treatment discontinuation. 9. Females must agree to abstain from breastfeeding during study participation and 150 days after study drug discontinuation. 10. Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 150 days following discontinuation from this study, even if he has undergone a successful vasectomy. 11. Males must also agree to refrain from donating semen or sperm during the treatment phase and for 150 days after discontinuation from this study treatment. 12. All subjects must agree to refrain from donating blood while on study therapy and for 28 days after discontinuation from this study treatment. Females of childbearing potential (FCBP): a female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months). \* The two methods of birth control used may be selected from the following categories, but the two methods cannot be selected from any one category: barrier method: i.e., condom (male or female) or diaphragm with spermicide; hormonal: i.e., contraceptive pill, patch; intrauterine device (IUD); vasectomy; or tubal ligation.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate (VGPR or better) defined by IMWG criteria | 100 days | To determine the response rate (VGPR or better) defined by IMWG criteria at 100 days (+/- 7 days) after the autologous stem cell transplant (ASCT). |
Countries
Canada
Outcome results
None listed