This is a single center, open-label, phase 2 study in elderly (age ≥ 70) subjects with newly diagnosed multiple myeloma who are transplant ineligible. Subjects will receive subcutaneous daratumumab, dose-attenuated bortezomib, revlimid, and dexamethasone until confirmed disease progression, discontinuation of study treatment due to unacceptable drug toxicity, or other reasons. Throughout the study, subjects will be monitored closely for adverse events, laboratory abnormalities, and clinical response.
This is a single center, open-label, phase 2 study in elderly (age ≥ 70) subjects with newly diagnosed multiple myeloma who are transplant ineligible. The main study consists of the following phases: a 28-day screening phase; followed by initial therapy with 12 cycles of daratumumab in combination with dose-attenuated VRd; and a maintenance phase that starts after Cycle 12 of therapy. Cycles are 28 days in length. Treatment can continue until disease progression or unacceptable toxicity. After 12 cycles of initial therapy, maintenance therapy will begin with 28 day cycles of daratumumab with either lenalidomide or ixazomib and the choice of maintenance therapy will be based on cytogenetic risk status at diagnosis. All subjects will continue maintenance treatment until disease progression, except maintenance daratumumab will be discontinued after 2 years if subjects remain on maintenance treatment at that time. All subjects will be followed in the longterm follow-up for at least 1 year after last dose of study treatment and will continue until death, withdrawal of consent for study participation, or the end of study definition is met. The end of study is defined as when all subjects have completed at least 1 year of long-term follow up and until death, withdrawal of consent for study participation, or 5 years after first patient begins daratumumab therapy, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
Daratumumab 1800 mg will be delivered by subcutaneous injection given through a syringe and needle by a manual push over approximately 3 to 5 minutes. Doses will be administered at alternating locations on the abdomen. Daratumumab will be administered weekly during treatment in Cycles 1 to 2, every 2 weeks during cycles 3-6, and every 4 weeks thereafter.
Subjects will receive 1.3 mg/m2 bortezomib as a subcutaneous infusion on Days 1, 8, and 15 during the 28-day cycles.
In Cycles 1 through 12, lenalidomide will be self-administered at a dose of 15 mg orally each day on Days 1 through 21 of each 28-day cycle. For subjects with CrCl 30-60mL/min, lenalidomide will be reduced to 10mg daily, and for subjects with CrCl 15-30 mL/min, lenalidomide will be reduced to 5mg daily. In maintenance phase: lenalidomide will be administered at one dose level below Cycles 1-12 dosing ie 10 mg orally daily. In maintenance, for subjects with CrCl 30-60 mL/min, lenalidomide will be reduced to 5 mg daily during maintenance treatment, and for subjects with CrCl 15-30 mL/min, lenalidomide will be reduced to 5 mg every other day during maintenance treatment.
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Responses: VGPR or better
≥ VGPR rate after 8 cycles of therapy, defined as the proportion of subjects who have achieved VGPR or better, according to the IMWG criteria.
Time frame: At the end of cycle 8, each cycle is 28 days
Overall Response Rates
ORR (≥PR), CBR (≥SD), ≥CR, and sCR rates defined as the proportion of subjects who achieve each of these response categories (or better response category) according to the IMWG criteria
Time frame: Within a year
Duration of ORR (≥PR), ≥VGPR, ≥CR, and sCR
Defined as the duration from the date of initial attainment of a response category (or better response category), according to the IMWG criteria, to the date of first documented evidence of relapse from CR (or sCR) or progressive disease (PD)
Time frame: Within two years
Time to Overall Response Rate
Defined as the duration from the date of initial therapy to the date of attainment of a response category and was subsequently confirmed by a repeated measurement as required by the IMWG criteria
Time frame: Within a year
Time to Progression
Defined as the duration from the date of initial therapy to the date of first documented evidence of progressive disease according to the IMWG criteria
Time frame: Within 2 years
Progression Free Survival
Defined as the duration from the date of initial therapy to the date of first documented evidence of PD or death, whichever comes first
Time frame: Within 5 years
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Dexamethasone will be self-administered orally at a total dose of 20 mg weekly during cycles. However, the dexamethasone 20 mg oral or IV (only if oral is not available) dose administered as a preinfusion medication on daratumumab infusion days replaces the oral dexamethasone dose for that day. Dexamethasone will be administered until the subject experiences disease progression or unacceptable toxicity. In the maintenance phase, dexamethasone/steroid premedications may be tapered or discontinued in the absence of daratumumab related infusion reactions/based on patient tolerance. In the event of persistent daratumumab related infusion reactions, the least amount of steroid premedications needed to prevent the same may be used.
During maintenance treatment, if choice of maintenance therapy includes ixazomib, ixazomib will be administered at 3 mg orally daily on Days 1,8, and 15 of each cycle. For subjects with CrCl 15-30 mL/min, ixazomib will be reduced to 2.3 mg once per week during maintenance treatment.
Overall Survival
Defined as the duration from the date of initial therapy to the date of the subject's death.
Time frame: Within 5 years
Number of Adverse Events
To assess safety and tolerability using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE Version 4.03)
Time frame: Within 5 years