Carfilzomib in Combination With Daratumumab, Lenalidomide and Dexamethasone in Transplant-ineligible NDMM Patients

Sponsor
Tel-Aviv Sourasky Medical Center
Study ID
NCT04065789
Phase
PHASE2
Status
Completed

Conditions

  • Myeloma Multiple
  • Myeloma, Plasma-Cell
  • Myeloma-Multiple
  • Plasma Cell Myeloma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Carfilzomib — DRUG
    Carfilzomib on Days 1, 8, 15, of cycle numbers 1-9 and Days 1 and 15 only of cycle numbers 10-18, at a dose of 20 mg/m2 on day 1 of cycle 1; at dose of 56 mg/m2 on all subsequent once weekly dosing days. The quadruple regimen treatment will be administered for 18 cycles.
  • Daratumumab — DRUG
    Daratumumab : 16 mg/Kg weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks thereafter. The quadruple regimen treatment will be administered for 18 cycles.
  • Lenalidomide — DRUG
    Lenalidomide (25 mg), administered on days 1-21 of 28-day cycle.In frail patients, Lenalidomide dose will be reduced according to 15 mg . The quadruple regimen treatment will be administered for 18 cycles.
  • Dexamethasone — DRUG
    Patients will be treated with IV or oral dexamethasone (20 mg for fit and INT-FIT, 10 mg for frail), administered on Days 1-2, 8-9, 15-16, and 22-23 of each 28-day cycle for cycles 1-2 followed by weekly 20 mg dexamethasone on subsequent cycles; In frail patients, dexamethasone will be reduced to 10 mg . The quadruple regimen treatment will be administered for 18 cycles.

Study Details

Patients with newly diagnosed multiple myeloma (NDMM) who failed to achieve at least a minimal response (MR) after 2 cycles or a partial response (PR), after 4 cycles of a bortezomib-containing therapy, or progress on therapy during first 4 cycles (response defined by international Myeloma Working Group \[IMWG\] criteria), will be treated with a quadruple regimen comprised of: Daratumumab 16 mg/Kg weekly during cycles 1-2, q14 days during cycles 3-6, thereafter monthly (1st dose cycle 1 may be split over 2 days); Once-weekly intravenous (IV) administration of Carfilzomib on days 1, 8, 15, of cycle numbers 1-9 and Days 1 and 15 only of cycle numbers 10-18, at a dose of 20 mg/m2 on day 1 of cycle 1; at dose of 56 mg/m2 on all subsequent once weekly dosing days, alongside concomitant treatment with twice-weekly IV or oral dexamethasone 20mg administered on Days 1-2, 8-9, 15-16, and 22-23 of a 28-day cycle, for cycles 1-2 followed by weekly 20 mg dexamethasone on subsequent cycles; and oral Lenalidomide 25 mg, administered on days 1-21 of a 28-day cycle. On treatment days that require both Carfilzomib and Daratumumab infusions, Carfilzomib will be administrated prior to Daratumumab administration. All patients will undergo frailty assessment based on IMWG recommendations, and will be classified as fit, intermediate-fit and frail. Frail patients will receive Lenalidomide dose adjustment to 15 mg (throughout the study, from cycle 1 and on), and dexamethasone at 10 mg x 2/week cycles 1-2 followed by 10 mg/week for subsequent cycles. The quadruple regimen will be administered for 18 cycles, followed by long-term follow-up in which patients will receive standard of care treatment with Lenalidomide/dexamethasone (Rd) treatment, unless disease progression, the physician decides otherwise, the patient suffers from unacceptable toxicity, withdraws consent, or dies (whichever occurs first).

Key Dates

Start date
May 2, 2018
Status verified
Jan 2022
Primary completion
Aug 27, 2021
Completion
Nov 12, 2021

Study Design

Enrollment
41 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Carfilzomib,Daratumumab,revlimid and dexamethasone
    Carfilzomib, Daratumumab, Lenalidomide, Dexamethasone

Primary Outcome Measure

Proportion of patients who experience any AE incidence, grade > 2 drug-elicited toxicities, peripheral neuropathy events (Grade 2 or higher). [ Time Frame: from screening through month 20 ]

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