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.

MULTIPLE MYELOMA (MM) Clinical Trial

— FORTE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02203643
• Other study ID #: UNITO-MM-01 / FORTE
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 2015
• Est. completion date: October 2033

Study information

• Verified date: November 2023
• Source: University of Turin, Italy
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 477
• Est. completion date: October 2033
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• MULTIPLE MYELOMA (MM)
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib

• Cyclophosphamide

• Lenalidomide

• Dexamethasone

Locations

Country	Name	City	State
Italy	IRCCS--CROB --CROB di Rionero in di Rionero in Vulture	Rionero in Vulture

Sponsors (1)

Lead Sponsor	Collaborator
Mario Boccadoro

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy in term of at least Very Good Partial Response (VGPR)	The efficacy, in term of at least VGPR, of the combination of carfilzomib, dexamethasone with cyclophosphamide or lenalidomide after 4 cycles of induction treatment in newly diagnosed MM patients eligible for ASCT.	Up to 2 years
Secondary	sCR rate	the stringent complete response (sCR) rate in the 3 arms after complete primary therapy (induction, ASCT and consolidation for the transplant arms and after 12 cycles in the long treatment arm) in an explorative manner.	up to 1 year
Secondary	Safety as incidence of grade 3/4 adverse events	the safety in the 3 induction/consolidation arms and in the 2 maintenance arms.	Up to 3 years
Secondary	Survival	the survival in the 3 induction/consolidation arms and in the 2 maintenance arms.	Up to 5 years
Secondary	Correlation between tumor response and outcome with baseline prognostic factors.		up to 5 years
Secondary	Minimal Residual Disease (MRD)	Minimal Residual Disease	up to 5 years
Secondary	Survival after relapse	the survival after relapse	up to 7 years