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.

NCT ID: NCT02203643

Last Updated: 2024-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

477 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-28

Study Completion Date

2026-03-26

Brief Summary

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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.

Detailed Description

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Conditions

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MULTIPLE MYELOMA (MM)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Interventions

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Carfilzomib

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Other Intervention Names

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Revlimid

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mario Boccadoro

OTHER

Sponsor Role lead

Responsible Party

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Mario Boccadoro

MD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Antonio Palumbo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Turin, Italy

Locations

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

Rionero in Vulture, , Italy

Site Status

Countries

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Italy

References

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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.

Reference Type DERIVED
PMID: 38849344 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38048557 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36528035 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35666982 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34774221 (View on PubMed)

Other Identifiers

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UNITO-MM-01 / FORTE

Identifier Type: -

Identifier Source: org_study_id