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Pretrial induction chemotherapy (if required): bortezomib, cyclophosphamid, dexamethasone (VCD).

Induction Chemotherapy: Daratumumab, Carfilzomib,Lenalidomide, Dexamethasone, CisPlatin, epirubicin, Cyclophosphamide and Etoposide (Dara-KRd-PACE).

Autologous Stem Cell Transplant (ASCT) : Melphalan, ASCT.

Consolidation: Daratumumab, Carfilzomib, Lenalidomide, Dexamethasone (Dara-KRd).

Maintenance: Daratumumab, Carfilzomib, and Dexamethasone (Dara-Kd).

Given by vein: days 1 and 8 of each Induction cycle; days 1 and 15 of each Consolidation cycle; and day 1of each Maintenance cycle.

Given by vein: days 1,2,8 and 9 of each Induction cycle; days 1, 2, 8, 9,15, and 16 of each Consolidation cycle; days 1, 2,15, and 16 of each Maintenance cycle.

Carfilzomib

Given by mouth: days 1-7 of each Induction cycle; days 1-14 of each Consolidation cycle.

Given by mouth or by vein: days 1, 8, 15, and 22 of each Induction cycle; days 1, 8, 15, and 22 of each Consolidation cycle; and days 1 and 15 of every cycle during Maintenance

Given by vein: days 1-4 of each Induction cycle

epirubicin

ASCT

given by subcutaneous injection: days 1, 4, 8, and 11 of pretrial induction chemotherapy

bortezomib

Chunyan Sun, MD

Jian Xu, MD

This study will assess whether the combination of daratumumab and carfilzomib-based Induction/Consolidation/Maintenance Therapy with ASCT improves the outcome of patients with ultra high-risk, newly diagnosed multiple myeloma

Survival outcomes for patients with newly diagnosed multiple myeloma (MM) have improved substantially in the past decades, due to the introduction of novel therapeutic strategies. Unfortunately, patients with ultra-high-risk MM, including "double-hit" MM, extramedullary MM (EMM), and primary plasma cell leukemia (pPCL), have a significantly worse prognosis and benefit less from current therapeutic strategies. This study aims to investigate whether a treatment regimen combining daratumumab and carfilzomib-based Induction/Consolidation/Maintenance Therapy with autologous stem cell transplantation (ASCT) can improve the survival outcomes of newly diagnosed, transplant-eligible, ultra high-risk multiple myeloma patients. In the study, participants will receive induction therapy with 2-4 cycles of Dara-KRd-PACE, followed by ASCT, 4 cycles of Dara-KRd consolidation, and then maintenance with 12 cycles of Dara-Kd.

Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma

Clinical Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma

2-year Progression-free survival of participants as determined by investigator assessment.

progression-free survival of participants as determined by investigator assessment.

overall survival of participants as determined by investigator assessment.

Overall response rate as determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.

Minimal Residual Disease (MRD) negativity rate as assessed by next generation sequencing.

complete response rate as determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.

determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.

graded according to the Common Terminology Criteria for Adverse Events v5

Wuhan Union Hospital, China

Professor

Enrolled patients received lenalidomide at a dose of 25 mg/d for 21 days and oral dexamethasone at a dose of 40 mg on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, responding patients not eligible for SCT continued until 8 cycles of full-dose LD, if tolerated, followed by a maintenance dose of single agent lenalidomide equal to 10 mg/d on days 1-21 of each 28-day cycle.

Patients responding after 4 cycles and eligible for SCT proceeded according to single Centre transplant policy. Patients not responding after 4 cycles or progressing during this treatment were considered off-study.

Lenalidomide, dexamethasone

Pellegrino Musto, MD

This is an open label, multicenter, exploratory, single arm, two-stage study aiming to explore efficacy and safety of lenalidomide and dexamethasone combination (LD) as first line therapy in previously untreated patients with primary Plasma Cell leukemia (PPCL).

The primary endpoint was response rate according to International Uniform Criteria; secondary endpoints were: i) time to progression (TTP), progression free survival (PFS, and overall survival (OS); ii) percentage of eligible PPCL patients able to mobilize and collect peripheral blood stem cells after LD treatment; iii) percentage of eligible PPCL patients able to undergo autologous or allogeneic stem cells transplantation after LD treatment; iv) serious/severe adverse event (SAEs) rate.

Lenalidomide and Dexamethasone in Primary Plasma Cell Leukemia

A Pilot Study of Lenalidomide and Dexamethasone in Patients With Primary Plasma Cell Leukemia

Number of eligible patients reaching stem cell transplantation procedure

Celgene Corporation

IRCCS Centro di Riferimento Oncologico della Basilicata

Onco-Hematology Department Director at IRCCS-CROB Rionero in Vulture, Italy

Biological: CART cells chimeric antigen receptor T cells

Biological:

chimeric antigen receptor T cells

Experimental: CAR-T cells Infusion

Juan Du

Juan Du, Ph.D

A Clinical Trial to Explore the Safety and Efficacy of CT071 injection in Patients with Relapsed/Refractory Multiple Myeloma or Primary Plasma Cell Leukemia

This trial is a single-arm, open-label, dose-finding, first-in-human clinical trial. The main aim of this study is to preliminarily evaluate the safety and tolerability of CT071 after infusion, and explore the dose range of CT071 in patients with relapsed/refractory multiple myeloma or primary plasma cell leukemia, so as to determine the possible recommended therapeutic dose (RD).

Study of CT071 Injection in RRMM or PPCL

A Clinical Trial to Explore the Safety and Efficacy of CT071 Injection in Patients With Relapsed/Refractory Multiple Myeloma or Primary Plasma Cell Leukemia

Evaluate DLT and adverse events after CT071 infusion

Cytokine release syndrome（CRS）should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading，higher scores mean a worse outcome.

An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cellassociated neurotoxicity syndrome (ICANS).

Levels of cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.

Serum concentrations of interleukin (IL)-2, IL-6，IL-8，IL-10，interferon-gamma (IFN-γ), and TNF-α after CT071 infusion

ORR defined as proportion of patients achieving PR or better based on IMWG defined response criteria

Rate of very good partial response (VGPR) and above defined as proportion of patients achieving VGPR or better based on IMWG defined response criteria;

Rate of complete response/stringent complete response (CR/sCR) defined as proportion of patients achieving CR or better based on IMWG defined response criteria.

DOR is defined as the time from first achieving PR or better to confirmed disease progression or death from any cause.

Minimal residual disease (MRD) negative rate is defined as the proportion of patients with VGPR or better who achieved 10-5 sensitivity of nucleated cell.

TTR defined as the time from the date of apheresis to the date of initial assessment of PR or better in patients with a best response assessment of partial response or better according to IMWG2016 criteria.

PFS defined as the time from the date of apheresis of the subject to the first assessment of confirmed disease progression or death from any cause according to IMWG2016 criteria, whichever occurs first.

OS defined as the time from the date of apheresis of the subject to death from any cause.

CARsgen Therapeutics Co., Ltd.

Shanghai Changzheng Hospital

Chief physician, professor

Hematologic Neoplasms

Dose Escalation followed a dose expansion.

Single group of patients for each indication (rrMM, RRpPCL).

CT071

CARsgen US

A Phase 1/2 Open label, multicenter, clinical trial of autologous CAR T-cell therapy targeting GPRC5D, in participants with relapsed/refractory multiple myeloma or relapsed/refractory primary plasma cell leukemia.

This is an open-label, multicenter, Phase 1/2 trial of CT071 in adult participants with relapsed or refractory multiple myeloma (RRMM) or relapsed or refractory primary plasma cell leukemia (RRpPCL).

The study will be conducted in two phases. Phase 1 of the study will be dose escalation followed by dose expansion. After recommended Phase 2 dose is identified in Phase 1, the enrollment of Phase 2 will start. Following consent, enrolled subjects will undergo apheresis to collect cells for manufacture of the CAR-T cells. Following the manufacture of the CAR-T cells, subjects will receive lymphodepletion prior to CAR T-cell infusion. All subjects who complete the study, as well as those who withdraw from the study after receiving CAR T-cell infusion for reasons other than death or meeting the early termination criteria, will be asked to undergo a 15-year long-term follow-up.

Phase 1; Dose escalation followed by dose expansion Phase 2; Single group of each indication will be dosed at the recommended dose level from Phase 1.

Anti-GPRC5D CAR-T Cells (CT071) in Participants With RRMM or RRpPCL

A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of CT071, an Autologous Anti-GPRC5D CAR T, in Relapsed/Refractory Multiple Myeloma (RRMM) or Relapsed/Refractory Primary Plasma Cell Leukemia (RRpPCL)

Frequency, type, and severity of AEs (SAEs, AESIs, laboratory abnormalities).

Objective response rate (ORR) per IMWG by IRC read; percentage of participants achieving confirmed PR or better per IMWG 2016 consensus criteria.

Overall Response Rate/Best Overall Response Rate by investigator (by IMWG stringent complete response/sCR, complete response/CR, very good partial response/VGPR, and partial response/PR by IRC and investigator assessment).

Duration of Response by IMWG (stringent complete response/sCR, complete response/CR, very good partial response/VGPR, and partial response/PR by IRC and investigator assessment).

Progression Free Survival by investigator assessment

Percentage of patients with anti-CT071 drug antibodies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma	NCT06140966	Multiple Myelom... Primary Plasma ... Extramedullary ...	Daratumumab Carfilzomib Lenalidomide Dexamethasone Cisplatin epirubicin Cyclophosphamid... Etoposide Melphalan ASCT bortezomib	18 Years - 70 Years	Wuhan Union Hospital, China
Lenalidomide and Dexamethasone in Primary Plasma Cell Leukemia	NCT01553357	Primary Plasma ...	Lenalidomide, d...	18 Years -	IRCCS Centro di Riferimento Oncologico della Basilicata
Study of CT071 Injection in RRMM or PPCL	NCT05838131	Multiple Myelom... Primary Plasma ...	Experimental: C...	18 Years -	Shanghai Changzheng Hospital
Lenalidomide and Dexamethasone in Primary Plasma Cell Leukemia	NCT01553357	Primary Plasma ...	Lenalidomide, d...	18 Years -	IRCCS Centro di Riferimento Oncologico della Basilicata
Anti-GPRC5D CAR-T Cells (CT071) in Participants With RRMM or RRpPCL	NCT06333509	Multiple Myelom... Primary Plasma ...	CT071	18 Years -	CARsgen Therapeutics Co., Ltd.

Spots Global Cancer Trial Database for primary plasma cell leukemia