Study of Carfilzomib Weekly Plus Melphalan and Prednisone in Untreated Symptomatic Elderly Multiple Myeloma (IFM2012-03)
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|ClinicalTrials.gov Identifier: NCT02302495|
Recruitment Status : Active, not recruiting
First Posted : November 27, 2014
Last Update Posted : June 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Carfilzomib||Phase 2|
Overall design. This study is a Multicenter, Open-label, Phase 2 study of Carfilzomib Weekly +MP in Untreated Elderly MM. Eligible patients must have a symptomatic, untreated MM with a measurable disease. There is a dose escalation part in the study as the MTD remained to be determined for carfilzomib weekly given for 4 infusions (day 1, 8, 15, 22) on a 35-days cycle.
This study will thus comprise 2 parts. Step 1. To determine MTD of Carfilzomib Weekly based on definition of DLTs - (N=6 patients per cohort, maximum 5 cohorts of carfilzomib weekly +MP) The patients will be included into three cohorts at 36 mg/m², 45 mg/m², 56 mg/m² and 70mg/m² of Carfilzomib Weekly given for 4 infusions (day 1, 8, 15, 22) +MP given on days 1 to 4 of a 35-days cycle. Carfilzomib will be administered at a dose of 36mg/m² for the first cohort where the 20 mg/m² dose is administered on Day 1 of Cycle 1 only and then 36 mg/m² for all subsequent doses.
If dose-limiting toxicities (DLTs) occur in fewer or equal than 2 of these patients, the next cohort of 6 patients (cohort 2) will be opened and patients will receive a dose of 20/45 mg/m². If DLTs occur in fewer or equal than 2 of the patients in cohort 2, the third cohort of 6 patients will receive a dose of 20/56 mg/m² where the 20 mg/m² dose is administered on Day 1 of Cycle 1 only and then 56 mg/m² for all subsequent doses. If DLTs occur in fewer or equal than 2 of the patients in cohort 3, the fourth and five cohort of 6 patients will receive a dose of 20/70 mg/m² where the 20 mg/m² dose is administered on Day 1 of Cycle 1 only and then 70 mg/m² for all subsequent doses.
If at any time during cycle 1 of a dose cohort, > 2 subjects experience a drug-related DLT, the MTD will have been exceeded, additional enrolment within the cohort will cease, and dose escalation will stop. The MTD will be defined as the dose level below which DLT is observed in > 33% (i.e. > 2 of 6) subjects in a cohort.
The following are defined as DLTs:
- Any hematologic toxicity of grade 4 intensity or preventing administration of 2 or more of the 4 carfilzomib doses of the first treatment cycle
- Grade ≥ 3 febrile neutropenia
- Grade ≥ 3 gastrointestinal toxicities
- Any other grade ≥ 3 nonhematologic toxicity considered related to CMP by the principal investigator.
- Grade ≥ 3 peripheral neuropathy persisting for more than 3 weeks after discontinuation of study drugs.
- grade 4 thrombocytopenia without bleeding lasting ≤ 7 days or
- grade 4 neutropenia lasting ≤ 7 days
- grade ≥ 3 nausea/ vomiting if the patient had not received adequate antiemetic prophylaxis Adverse events (AEs) will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). MTD determination will be based on occurrence of DLTs during the first induction treatment cycle only.
Step 2. Expanded Cohort (N=50 patients; Carfilzomib weekly at the MTD +MP only) After identification of the MTD, it is planned for the dose cohort to be expanded to include up to a total of 50 patients treated at the MTD of carfilzomib weekly for the step 2 of the study. A full treatment course is the same as for step 1, see "dosing regimen".
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Open Label Phase 2 Study of Carfilzomib Weekly Plus Melphalan and Prednisone in Untreated Symptomatic Elderly Multiple Myeloma|
|Actual Study Start Date :||January 2014|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2021|
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.
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.
- Dose Maximum Tolerate of Carfilzomib Weekly [ Time Frame: 35 days ]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.
- number of patients who reach Very Good Partial Response and Complete [ Time Frame: 315 days ]Expanded cohort, the primary endpoint is the Very Good Partial Response and Complete Response rate of Carfilzomib Weekly at the Maximum Tolerate Dosing and melphalan prednisone at the end of the 9 induction cycles using International Myeloma Working Group response criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02302495
|Study Chair:||Leleu Xavier, MD, PhD||University Hospital|