Carfilzomib, Cyclophosphamide and Dexamethasone In Newly Diagnosed Multiple Myeloma Patients (CCD)
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|ClinicalTrials.gov Identifier: NCT01346787|
Recruitment Status : Active, not recruiting
First Posted : May 3, 2011
Last Update Posted : August 2, 2018
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE||Phase 2|
Hide Detailed Description
This protocol is a phase II multicenter, international, non-comparative, open label study designed to jointly assess the safety and the efficacy of the association Carfilzomib with Cyclophosphamide and Dexamethasone (CCd) as induction treatment and Carfilzomib alone as maintenance in newly diagnosed MM patients.
Patients will be evaluated at scheduled visits in up to 4 study periods: pre-treatment, treatment, maintenance and long-term follow-up.
The pre-treatment period includes screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the availability of inclusion criteria described above.
The treatment period includes administration of Carfilzomib, Cyclophosphamide and Dexamethasone for 9 4-week courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled Carfilzomib administration. The response will be assessed after each 4-week cycle.
The maintenance period includes carfilzomib alone on days 1, 2, 15, 16 at 36mg/m2. For patients who show evidence of progression during maintenance phase, the frequency of Carfilzomib can be increased to days 1, 2, 8, 9, 15, 16 at the discretion of the investigator. It will be initiated at the end of the 9th course and will be stopped at progression or intolerance. The median expected duration of the maintenance treatment is approximately 2 years.
The Long Term Follow Up periods will start after development of confirmed Progression Disease, all patients are to be followed for survival during the Long Term Follow Up period every 3 months via telephone or office visit.
Approximately 15 Italian centers and foreign centers will participate to the protocol.
Patients with symptomatic newly diagnosed MM whose age is ≥ 65 years or who are ineligible for autologous stem cell transplantation. Up to 53 patients will be enrolled from different centers.
The duration of the treatment is approximately 9 months. This length of time is required to complete 9 courses of CCd. At the end of the first stage (19 patients), the trial will be temporarily stopped until all 19 patients complete the toxicity and efficacy evaluation (3 cycle): if there are more than 7 responses and less than 8 toxicities, a further group of 34 patients (total=53) will be enrolled. Otherwise, the trial will be definitively stopped or the DSMC will recommend testing other doses of the drugs.
The maintenance period in both phases will start at the end of the 9th course and will be stopped at progression or intolerance. The median expected duration of the maintenance treatment is approximately 2 years. The duration of follow-up from relapse will be approximately 2 years. The occurrence of PD will determine the duration of TTP of each patient. The occurrence of death will determine the duration of overall survival. The first analysis to evaluate safety and efficacy is planned when the 19 patients enrolled in the first stage of the study have completed the third cycle of induction treatment.
The trial will be stopped if there are < 6 responses, or > 9 toxicities or the Data Safety Monitoring Committee recommends testing other doses of the drugs; Otherwise, a further group of 34 patients (total=53) will be enrolled. The final conclusion will be negative if there are ≤ 23/53 responses, or ≥ 20/53 drug-related toxicities.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A MULTICENTER, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS|
|Actual Study Start Date :||July 2011|
|Actual Primary Completion Date :||October 2012|
|Estimated Study Completion Date :||October 2019|
Experimental: Carfilzomib Cyclophosphamide Dexamethasone
The treatment period includes administration of Carfilzomib Cyclophosphamide Dexamethasone for 9 courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled carfilzomib administration. The response will be assessed after each cycle.
Drug: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE
Patients will start induction treatment with Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15. Low dose Dexamethasone will be given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23. Carfilzomib = 20 mg/m2 IV once daily on days 1, 2, of cycle 1 only followed by 36 mg/ m2 days 8, 9, 15, 16 in cycle 1, then for all subsequent doses 36 mg/ m2 IV once daily on days 1, 2, 8, 9, 15, 16, followed by 13-day rest period (day 17 through 28). Each cycle will be repeated every 28 days for a total of 9 courses. MANTEINANCE PERIOD At the end of induction phase (9 courses), maintenance phase with Carfilzomib alone IV at 36 mg/ m2 IV on days 1, 2, 15, 16 will start, until progression or intolerance. For patients who show evidence of progression during maintenance phase, the frequency of Carfilzomib can be increased to days 1, 2, 8, 9, 15, 16 at the discretion of the investigator, or the patient may be removed from the study
- Toxicity: Assessment of adverse events will be performed at the end of third cycle according to the National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE version 4.0) [ Time Frame: 4 years ]Toxicity is defined as the first occurrence of a grade 4 hematologic drug-related toxicity excluding anemia, (grade 4 neutropenia must last longer than 3 days and grade 4 thrombocytopenia must last longer than 7 days in order to be considered a toxicity) with the exception of (grade 4 neutropenia > 3 days , or grade 4 thrombocytopenia >7 days duration) or grade 3 non-hematologic drug-related toxicity.
- Efficacy will be assessed by considering partial response (PR) following the proposed regimen. Assessment of Partial Response rate will be performed at the end of third cycle according to the criteria of the International Myeloma Working Group. [ Time Frame: 4 years ]
- Response rate [ Time Frame: 4 years ]
- Duration of Progression Free Survival [ Time Frame: 4 years ]
- Time to progression (TTP) [ Time Frame: 4 years ]
- Duration of Response (DOR) [ Time Frame: 4 years ]
- Duration of Overall Survival [ Time Frame: 4 years ]
- Time to next therapy [ Time Frame: 4 years ]
- Progressio Free Survival [ Time Frame: 4 years ]Relation between responses and Progression Free Survival, in responding and non-responding patients.
- β2-microglobulin as prognostic factors [ Time Frame: 4 years ]Subgroups analysis on prognostic factors
- peripheral neuropathy [ Time Frame: 4 years ]Rates of peripheral neuropathy, according to the National Cancer Institute Common Toxicity Criteria (version 4.0)
- Progression Free Survival [ Time Frame: 4 years ]Effect on Progression Free Survival of maintenance with low dose of Carfilzomib (days 1 and 2 every other week)
- C reactive protein as prognostic factors [ Time Frame: 4 years ]Subgroups analysis on prognostic factors
- cytogenetics as prognostic factors [ Time Frame: 4 years ]Subgroups analysis on prognostic factors
- microRNA [ Time Frame: 4 years ]Subgroups analysis on prognostic factors
- gene expression profile [ Time Frame: 4 years ]Subgroups analysis on prognostic factors
- Overall Survival [ Time Frame: 4 years ]Effect on Overall Survival of maintenance with low dose of Carfilzomib (days 1 and 2 every other week)
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): NCT01346787
|IRCCS CROB UOC di Ematologia e trapianto cellule staminali Ospedale Oncologico Regionale|
|Rionero In Vulture, PZ, Italy, 85100|
|azienda ospedaliero-universitaria umberto I Clinica di Ematologia|
|Ancona, Italy, 60020|
|Policlinico S. Orsola Istituto di Ematologia e Oncologia Medica|
|Bologna, Italy, 40138|
|Ospedale Ferrarotto_Reparto di Ematologia|
|Catania, Italy, 95124|
|Az.Osp. Di Careggi_Dh ematologia|
|Firenze, Italy, 50134|
|Istituto Nazionale per lo Studio e la Cura dei Tumori_UO Ematologia_Trapianto di Midollo Osseo Allogenico|
|Milano, Italy, 20133|
|Divisione di Ematologia Dipartimento di Medicina Clinica e Sperimentale Università Amedeo Avogadro|
|Novara, Italy, 28100|
|Cattedra di ematologia Università La Sapienza|
|Divisione di ematologia ospedale s.eugenio|
|S.C.di Oncoematologia, Azienda Ospedaliera S. Maria di Terni|
|Az. Osp. San Giovanni Battista - Molinette_Ematologia 2|
|Torino, Italy, 10126|
|Division of Hematology, A.O.U. San Giovanni Battista|
|Torino, Italy, 10126|