Clinical trial NCT02203643: Evaluation of the Safety and the Efficacy of Carfilzomib Combined With Cyclophosphamide and Dexamethasone (CCyd) or Lenalidomide and Dex (CRd) Followed by ASCT or 12 Cycles of Carf Combined With Dex and Len for Patients Eligible for ASCT With Newly Diagnosed Multiple Myeloma.
Official title: A MULTICENTER, RANDOMIZED, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE (CCyd) as Pre Transplant INDUCTION and Post Transplant Consolidation or CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE (CRd) as Pre Transplant INDUCTION and Post Transplant Consolidation or Continuous Treatment With CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE (12 Cycles) Without Transplant, All Followed by MAINTENANCE With LENALIDOMIDE (R) Versus LENALIDOMIDE AND CARFILZOMIB (CR) IN NEWLY DIAGNOSED MULTIPLE MYELOMA (MM) PATIENTS ELEGIBLE FOR AUTOLOGOUS TRANSPLANT
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: MULTIPLE MYELOMA (MM)
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2014-07-30
Enrollment: 477
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and the efficacy of carfilzomib combined with cyclophosphamide and dexamethasone (CCyd) or lenalidomide and dexamethasone (CRd) followed by autologous transplantation ASCT or 12 cycles of carfilzomib combined with dexamethasone and lenalidomide for patients eligible for ASCT with newly diagnosed multiple myeloma. As a secondary endpoint this study will evaluate the best maintenance treatment between lenalidomide and lenalidomide combined with carfilzomib.

Four hundred seventy-seven patients, males and females aged \> 18 years, enrolled in several sites, will take part in this study.

The duration of the study is approximately 5 years.


Eligibility criteria: Inclusion Criteria:

Age ≥ 18 years Newly diagnosed MM based on standard CRAB criteria (see appendix B). Patient \< 65 years eligible for ASCT. Patient has measurable disease according to IMWG (International Myeloma Working Group) criteria.

Patient has given voluntary written informed consent. Patient agrees to use acceptable methods for contraception. Patient has a Karnofsky performance status ≥ 60%

Pretreatment clinical laboratory values within 30 days of enrolment:

Platelet count ≥50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is \> 50%) Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors Corrected serum calcium ≤14 mg/dL (3.5 mmol/L) Alanine transaminase (ALT): ≤ 3 x the Upper Limit Normal (ULN) Total bilirubin: ≤ 2 x the ULN Calculated or measured creatinine clearance: ≥ 30 mL/minute. LVEF≥40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available Life expectancy ≥ 3 months

Exclusion Criteria:

Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid \< to the equivalent of dexamethasone 40 mg/day for 4 days) Patients with non-secretory MM unless serum free-light chains are present and the ratio is abnormal or a plasmocytoma with minimum largest diameters of \> 2 cm Patients ineligible for autologous transplantation Pregnant or lactating females

Presence of:

Clinical active infectious hepatitis type A, B, C or HIV Acute active infection requiring antibiotics or infiltrative pulmonary disease Myocardial infarction or unstable angina ≤ 4 months or other clinically significant heart disease Peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 4.0 Known history of allergy to Captisol ® (a cyclodextrin derivative used to solubilize carfilzomib) Contraindication to any of the required drugs or supportive treatments Invasive malignancy within the past 3 years Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the enrolment or place the subject at unacceptable risk.

Primary outcomes:
measure: Efficacy in term of at least Very Good Partial Response (VGPR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: sCR rate
timeFrame: up to 1 year
measure: Safety as incidence of grade 3/4 adverse events
timeFrame: Up to 3 years
measure: Survival
timeFrame: Up to 5 years
measure: Correlation between tumor response and outcome with baseline prognostic factors.
timeFrame: up to 5 years
measure: Minimal Residual Disease (MRD)
timeFrame: up to 5 years
measure: Survival after relapse
timeFrame: up to 7 years
Other outcomes:
Locations:
city: Rionero in Vulture
country: Italy
facility: IRCCS--CROB --CROB di Rionero in di Rionero in Vulture
Study officials:
affiliation: University of Turin, Italy
name: Antonio Palumbo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bertamini L, Oliva S, Rota-Scalabrini D, Paris L, More S, Corradini P, Ledda A, Gentile M, De Sabbata G, Pietrantuono G, Pascarella A, Tosi P, Curci P, Gilestro M, Capra A, Galieni P, Pisani F, Annibali O, Monaco F, Liberati AM, Palmieri S, Luppi M, Zambello R, Fazio F, Belotti A, Tacchetti P, Musto P, Boccadoro M, Gay F. High Levels of Circulating Tumor Plasma Cells as a Key Hallmark of Aggressive Disease in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2022 Sep 20;40(27):3120-3131. doi: 10.1200/JCO.21.01393. Epub 2022 Jun 6.
citation: Gay F, Musto P, Rota-Scalabrini D, Bertamini L, Belotti A, Galli M, Offidani M, Zamagni E, Ledda A, Grasso M, Ballanti S, Spadano A, Cea M, Patriarca F, D'Agostino M, Capra A, Giuliani N, de Fabritiis P, Aquino S, Palmas A, Gamberi B, Zambello R, Petrucci MT, Corradini P, Cavo M, Boccadoro M. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial. Lancet Oncol. 2021 Dec;22(12):1705-1720. doi: 10.1016/S1470-2045(21)00535-0. Epub 2021 Nov 11.