Study of Carfilzomib Weekly Plus Melphalan and Prednisone in Untreated Symptomatic Elderly Multiple Myeloma

NCT02302495 | Completed Phase 2

• 2 other identifiers: 2012_322012-004490-10
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 33

Brief Summary

IFM 2012-03 protocol is a Phase 2 multicenter nonrandomized open in elderly patients with multiple myeloma at diagnosis. Study primary objectives are in the first step to determine Maximum tolerated dose (MTD) of Carfilzomib Weekly based on definition of Dose-limiting toxicities (DLTs) and in the second step to expanded cohort, to determine the VGPR (Very Good Partial Response) + CR (Complete Response) rate of Carfilzomib Weekly at the MTD in combination with Melphalan Prednisone at the end of the 9 induction cycles.

Conditions

Multiple Myeloma

Keywords

Carfilzomib weekly; and Melphalan and Prednisone

Outcome Measures

Primary Outcomes (1)

• Dose Maximum Tolerate of Carfilzomib Weekly

  If dose-limiting toxicities occur in fewer than 3 of these patients per cohort, the next cohort of 6 patients (cohort 2,3 and 4) will be open. If at any time during cycle 1 of a dose cohort, \> 2 subjects experience a drug-related dose-limiting toxicities, the Maximum Tolerate Dosing will have been exceeded, additional enrolment within the cohort will cease, and dose escalation will stop. The Maximum Tolerate Dosing will be defined as the dose level below which dose-limiting toxicities is observed in \>33% subjects in a cohort.

  35 days

Secondary Outcomes (1)

• number of patients who reach Very Good Partial Response and Complete

  315 days

Study Arms (1)

Carfilzomib weekly+Melphalan+Prednisone

OTHER

one arm, two steps and two parts.In the first step of the study: 5 cohorts of 6 patients with Carfilzomib weekly administrated at different dose regimen will be opened one after the other to determine Maximum tolerated dose of Carfilzomib based on definition of Dose-limiting toxicities.In the second step of the study:expanded Cohort, 50 patients received Carfilzomib at the MTD. In Part 1. Induction.Nine 5 weeks cycles of weekly CMP are plannedCarfilzomib. 36, 45, 56 or 70 mg/m² on days 1, 8, 15, 22 IV route . Patients will start the first cycle day 1 with 20mg/m². In combination with oral Melphalan 0.25mg/kg/j and oral prednisone 60mg/m², both on days 1 to 4.Part 2. Maintenance.Carfilzomib. 36 mg/m² weekly, every two weeks IV route for 1 year.

Drug: Carfilzomib

Interventions

Carfilzomib DRUG

DOSING REGIMEN. The regimen will have 2 parts: Part 1. Induction. Nine 5 weeks cycles (35-days each) of weekly Carfilzomib Melphalan Prednisone are planned Carfilzomib. 36, 45, 56 or 70 mg/m² on days 1, 8, 15, 22 IV route followed by a 13-day rest period per 35-days cycle. Patients will start the first cycle day 1 with 20mg/m². In combination with oral Melphalan 0.25mg/kg/j and oral prednisone 60mg/m², both on days 1 to 4. Part 2. Maintenance. Carfilzomib. 36 mg/m² weekly, every two weeks IV route for 1 year. Melphalan and Prednisone is not pursued at this phase of the study.

Also known as: Melphalan, Prednisone

Carfilzomib weekly+Melphalan+Prednisone

Eligibility Criteria

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

You may qualify if:

• able to understand and voluntarily sign an informed consent form
• able to adhere to the study visit schedule and other protocol requirements.
• age ≥ 65 years.
• life expectancy \> 6 months.Patients must have Symptomatic Measurable previously Untreated MM
• have measurable disease as defined by the following: quantifiable monoclonal M-component value in the serum and/or urine
• eastern Cooperative Oncology Group performance status score ≤2
• dequate bone marrow function, documented within 72 hours and without transfusion 5 days prior to the first intake of investigational product no growth factor support Adequate organ function
• subjects affiliated with an appropriate social security system.
• male subjects must:Understand the potential teratogenic,and genotoxic risk of Melphalan if engaged in sexual activity with a pregnant female or a female of childbearing potential.
• understand the potential genotoxic risk of Carfilzomib if engaged in sexual activity with a pregnant female or a female of childbearing potential.
• practice complete abstinence or understand the need and agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential throughout the entire duration of study treatment, during dose interruptions and until at least 3 months after the end of treatment discontinuation of CMP, even if he has undergone a successful vasectomy.
• if pregnancy or a positive pregnancy test does occur in the partner of a male study patient during study participation, the investigator must be notified immediately.
• agree not to donate semen or sperm during study drug therapy and until at least 3 months after the end of treatment discontinuation of CMP.

You may not qualify if:

• any other uncontrolled medical condition or comorbidity that might interfere with subject's participation.
• known positive for HIV or active infectious hepatitis, type B or C.
• patient with terminal renal failure that require dialysis and clearance creatinine \< 30 ml/min.
• prior history of malignancies, other than multiple myeloma, unless the patients has been free of the disease for ≥ 5 years.
• prior local irradiation within two weeks before first dose
• evidence of central nervous system (CNS) involvement.
• unable to take corticotherapy at study entry
• any ongoing adverse event or medical history \> grade 2 severity
• persons protected by a legal regime (guardianship, trusteeship).Alkeran's (Melphalan) contraindication: Hypersensitivity to Melphalan or to any other constituents.
• patients with heart failure class 3 and 4 according to the NYHA criteria, or patients with past history of myocardial infarction within the last 6 months or no controlled cardiac conduction abnormalities.
• patients with a left ventricular ejection fraction under or equal to 45 % (LVEF ≤ 45%)

Sponsors & Collaborators

• University Hospital, Lille: lead
• Amgen: collaborator

Study Sites (33)

Centre Hospitalier H. Duffaut

Avignon, 84902, France

Location

Centre Hospitalier de la côte basque

Bayonne, 64109, France

Location

Hôpital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33300, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, 71100, France

Location

Centre Hospitalier de Chambery

Chambéry, 73011, France

Location

Hôpital St Antoine Béclére

Clamart, 92140, France

Location

CH Louis Pasteur

Colmar, 68024, France

Location

CH Francilien

Corbeil-Essonnes, 91106, France

Location

CHU Henri Mondor

Créteil, 94010, France

Location

Hématologie Clinique, CHU, Hôpital d'Enfants

Dijon, 21000, France

Location

Centre hospitalier départemental La Roche sur Yon

La Roche-sur-Yon, 85025, France

Location

Centre Jean Bernard

Le Mans, 72000, France

Location

Hôpital St Vincent de Paul - GH-ICL

Lille, 59020, France

Location

Chru Lille

Lille, 59037, France

Location

CHU de Limoges

Limoges, 87000, France

Location

Hématologie, Institut Paoli Calmette

Marseille, 13273, France

Location

CH Meaux

Meaux, 77104, France

Location

Hôpital Notre Dame de Bon Secours

Metz, 57038, France

Location

Hopital J Monod

Montivilliers, 76290, France

Location

Hôpital E Muller

Mulhouse, 68100, France

Location

CHRU, Hôtel Dieu

Nantes, 44035, France

Location

Centre de NICE 2/ Hôpital Archet

Nice, 06202, France

Location

CHU Nimes CAREMEAU

Nîmes, 30029, France

Location

Hôpital St Antoine

Paris, 75571, France

Location

Groupe hospitalier Pitié Salpétrière

Paris, 75651, France

Location

Hôpital Haut-Leveque

Pessac, 33604, France

Location

Unité de Recherche Clinique - CH Perigueux

Périgueux, 24019, France

Location

Centre Hospitalier Lyon Sud -1

Pierre-Bénite, 69495, France

Location

Hématologie Clinique, Hôpital Robert Debré, CHU Reims

Reims, 51092, France

Location

Hématologie, IUCT oncopole

Toulouse, 31059, France

Location

CHRU, Hôpitaux de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Melphalan; Prednisone

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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Leleu Xavier, MD, PhD

  University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2014
• First Posted: November 27, 2014
• Study Start: January 8, 2014
• Primary Completion: July 17, 2016
• Study Completion: July 31, 2021
• Last Updated: December 8, 2025

Record last verified: 2025-12

Locations

FR (33)