NCT04065789: KyDaR

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

Completed Phase 2 Last updated 27 January 2022

What this trial tests

Phase 2 trial testing Carfilzomib in Myeloma Multiple in 41 participants. Completed in 12 November 2021.

Timeline

2 May 2018

Primary endpoint
27 August 2021

12 November 2021

Quick facts

Lead sponsor	Tel-Aviv Sourasky Medical Center
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	41
Start date	2 May 2018
Primary completion	27 August 2021
Estimated completion	12 November 2021
Sites	14 locations across Israel

Drugs / interventions tested

• Carfilzomib (carfilzomib) — full drug profile →
• Daratumumab (daratumumab) — full drug profile →
• Lenalidomide — full drug profile →
• Dexamethasone (dexamethasone) — full drug profile →

Conditions studied

• Myeloma Multiple — all drugs for Myeloma Multiple →
• Myeloma, Plasma-Cell — all drugs for Myeloma, Plasma-Cell →
• Myeloma-Multiple — all drugs for Myeloma-Multiple →
• Plasma Cell Myeloma — all drugs for Plasma Cell Myeloma →

Sponsor

Tel-Aviv Sourasky Medical Center

Who can join

18 and older, any sex, with Myeloma Multiple or Myeloma, Plasma-Cell. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Identification of resistance pathways and therapeutic targets in relapsed multiple myeloma patients through single-cell sequencing.
   Cohen YC, Zada M, Wang SY, Bornstein C, et al · · 2021 · cited 192× · PMID 33619369 · DOI 10.1038/s41591-021-01232-w
2. Multiple Myeloma Therapy: Emerging Trends and Challenges.
   Dima D, Jiang D, Singh DJ, Hasipek M, et al · · 2022 · cited 51× · PMID 36077618 · DOI 10.3390/cancers14174082
3. Single-cell RNA sequencing in osteoarthritis.
   Gu Y, Hu Y, Zhang H, Wang S, et al · · 2023 · cited 38× · PMID 37317049 · DOI 10.1111/cpr.13517
4. Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.
   Pakjoo M, Ahmadi SE, Zahedi M, Jaafari N, et al · · 2024 · cited 24× · PMID 38331801 · DOI 10.1186/s12964-023-01433-5
5. Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.
   Leonardo-Sousa C, Carvalho AN, Guedes RA, Fernandes PMP, et al · · 2022 · cited 21× · PMID 35408601 · DOI 10.3390/molecules27072201
6. Novel Insights into the Initiation, Evolution, and Progression of Multiple Myeloma by Multi-Omics Investigation.
   Gong L, Qiu L, Hao M. · · 2024 · cited 6× · PMID 38339250 · DOI 10.3390/cancers16030498
7. Multiple Myeloma Insights from Single-Cell Analysis: Clonal Evolution, the Microenvironment, Therapy Evasion, and Clinical Implications.
   Li S, Liu J, Peyton M, Lazaro O, et al · · 2025 · cited 5× · PMID 40002248 · DOI 10.3390/cancers17040653
8. Current perspectives on interethnic variability in multiple myeloma: Single cell technology, population pharmacogenetics and molecular signal transduction.
   Gandhi M, Bakhai V, Trivedi J, Mishra A, et al · · 2022 · cited 3× · PMID 36103755 · DOI 10.1016/j.tranon.2022.101532