FORTE: 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.

Sponsor
Mario Boccadoro (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02203643
Collaborator
(none)
477
Enrollment
1
Location
3
Arms
92
Duration (Months)
5.2
Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
477 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Feb 1, 2015
Actual Primary Completion Date :
Oct 1, 2016
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: CCyd

Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment. After the end of consolidation all patients will be randomized to receive: Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.

Drug: Carfilzomib

Drug: Cyclophosphamide

Drug: Dexamethasone

Experimental: CRd

Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment. After the end of consolidation all patients will be randomized to receive: Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.

Drug: Carfilzomib

Drug: Lenalidomide
Other Names:
  • Revlimid
  • Drug: Dexamethasone

    Experimental: CRd long treatment

    Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. Stem cells collection will be performed. Carfilzomib Lenalidomide and Dexamethasone administered for 8 28-day cycles. After that all patients will be randomized to receive: Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.

    Drug: Carfilzomib

    Drug: Lenalidomide
    Other Names:
  • Revlimid
  • Drug: Dexamethasone

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy in term of at least Very Good Partial Response (VGPR) [Up to 2 years]

      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.

    Secondary Outcome Measures

    1. sCR rate [up to 1 year]

      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.

    2. Safety as incidence of grade 3/4 adverse events [Up to 3 years]

      the safety in the 3 induction/consolidation arms and in the 2 maintenance arms.

    3. Survival [Up to 5 years]

      the survival in the 3 induction/consolidation arms and in the 2 maintenance arms.

    4. Correlation between tumor response and outcome with baseline prognostic factors. [up to 5 years]

    5. Minimal Residual Disease (MRD) [up to 5 years]

      Minimal Residual Disease

    6. Survival after relapse [up to 7 years]

      the survival after relapse

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1IRCCS--CROB --CROB di Rionero in di Rionero in VultureRionero in VultureItaly85028

    Sponsors and Collaborators

    • Mario Boccadoro

    Investigators

    • Principal Investigator: Antonio Palumbo, MD, University of Turin, Italy

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mario Boccadoro, MD, University of Turin, Italy
    ClinicalTrials.gov Identifier:
    NCT02203643
    Other Study ID Numbers:
    • UNITO-MM-01 / FORTE
    First Posted:
    Jul 30, 2014
    Last Update Posted:
    Apr 29, 2021
    Last Verified:
    Apr 1, 2021

    Study Results

    No Results Posted as of Apr 29, 2021