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.

NCT02203643 | Completed Phase 2 DMC

• 1 other identifier: UNITO-MM-01 / FORTE
• Study Type: interventional
• Target: 477
• Locations: 1 country
• Sites: 1

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.

Conditions

MULTIPLE MYELOMA (MM)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• sCR rate

  up to 1 year

• Safety as incidence of grade 3/4 adverse events

  Up to 3 years

• Survival

  Up to 5 years

• Correlation between tumor response and outcome with baseline prognostic factors.

  up to 5 years

• Minimal Residual Disease (MRD)

  up to 5 years

Study Arms (3)

CCyd

EXPERIMENTAL

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

CRd

EXPERIMENTAL

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; Drug: Dexamethasone

CRd long treatment

EXPERIMENTAL

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; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

CCyd; CRd; CRd long treatment

Cyclophosphamide DRUG

CCyd

Lenalidomide DRUG

Also known as: Revlimid

CRd; CRd long treatment

Dexamethasone DRUG

CCyd; CRd; CRd long treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mario Boccadoro: lead

Study Sites (1)

IRCCS--CROB --CROB di Rionero in di Rionero in Vulture

Rionero in Vulture, 85028, Italy

Location

Related Publications (5)

• D'Agostino M, Rota-Scalabrini D, Belotti A, Bertamini L, Arigoni M, De Sabbata G, Pietrantuono G, Pascarella A, Tosi P, Pisani F, Pescosta N, Ruggeri M, Rogers J, Olivero M, Garzia M, Galieni P, Annibali O, Monaco F, Liberati AM, Palmieri S, Stefanoni P, Zamagni E, Bruno B, Calogero RA, Boccadoro M, Musto P, Gay F. Additional copies of 1q negatively impact the outcome of multiple myeloma patients and induce transcriptomic deregulation in malignant plasma cells. Blood Cancer J. 2024 Jun 7;14(1):94. doi: 10.1038/s41408-024-01075-x.

  PMID: 38849344 DERIVED

• D'Agostino M, Bertuglia G, Rota-Scalabrini D, Belotti A, More S, Corradini P, Oliva S, Ledda A, Grasso M, Pavone V, Ronconi S, Vincelli ID, Ballanti S, Velluti C, Cellini C, Gozzetti A, Palmas AD, Gamberi B, Mancuso K, Paris L, Zambello R, Petrucci MT, Bruno B, Musto P, Gay F. Predictors of unsustained measurable residual disease negativity in patients with multiple myeloma. Blood. 2024 Feb 15;143(7):592-596. doi: 10.1182/blood.2023022080.

  PMID: 38048557 DERIVED

• Mina R, Musto P, Rota-Scalabrini D, Paris L, Gamberi B, Palmas A, Aquino S, de Fabritiis P, Giuliani N, De Rosa L, Gozzetti A, Cellini C, Bertamini L, Capra A, Oddolo D, Vincelli ID, Ronconi S, Pavone V, Pescosta N, Cea M, Fioritoni F, Ballanti S, Grasso M, Zamagni E, Belotti A, Boccadoro M, Gay F. Carfilzomib induction, consolidation, and maintenance with or without autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: pre-planned cytogenetic subgroup analysis of the randomised, phase 2 FORTE trial. Lancet Oncol. 2023 Jan;24(1):64-76. doi: 10.1016/S1470-2045(22)00693-3. Epub 2022 Dec 14.

  PMID: 36528035 DERIVED

• 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.

  PMID: 35666982 DERIVED

• 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.

  PMID: 34774221 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Cyclophosphamide; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Antonio Palumbo, MD

  University of Turin, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 30, 2014
• First Posted: July 30, 2014
• Study Start: February 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: March 30, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

IT (1)