Carfilzomib + Lenalidomide and Dexamethasone for BTK Inhibitors Relapsed-refractory or Intolerant MCL
- Conditions
- Mantle Cell Lymphoma
- Interventions
- Registration Number
- NCT03891355
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- Brief Summary
This is a prospective, multicenter, single arm, phase II trial designed to evaluate activity and the safety of the combination of Carfilzomib (K), Lenalidomide (R) and Dexamethasone (D) in patients with mantle cell lymphoma (MCL) relapsed/refractory (R/R) or intolerant to BTK inhibitor (BTKi) monotherapy or BTKi containing regimens with active disease necessitating treatment.
- Detailed Description
This is a prospective, multicenter, single arm, phase II trial designed to evaluate the safety and efficacy of the combination of Carfilzomib (K), Lenalidomide (R) and Dexamethasone (D) in patients with mantle cell lymphoma (MCL) relapsed/refractory (R/R) or intolerant to BTK inhibitor (BTKi) monotherapy or BTKi containing regimens.
The primary endpoint will be assessed 12 months after the start of treatment of the last patient. However, responsive patients (CR, PR, SD) may continue to receive K up to a maximum of 24 cycles and RD up to a maximum of 24 cycles. Patients who will interrupt therapy (for any reason) will be followed up to 12 months after the end of the treatment.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 16
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Carfilzomib (K) plus Lenalidomide (R) and Dexamethasone (D) Carfilzomib Carfilzomib (K) (maximum period of treatment= 24 cycles) * K on days 1-2, 8-9, 15-16 during cycles 1-12. The dosage of K will be 20 mg/m2 10' iv infusion on day 1 and 2 during cycle 1 and then 27 mg/m2 10' iv infusion thereafter; * K: on days 1-2, 15-16 during cycles 13-24. The dosage of K will be 27 mg/m2 10' iv infusion. Lenalidomide (R) (maximum period of treatment= 24 cycles) * R: 25 mg/daily on day 1 to 21 of a 28 days course; for patients with creatinine clearance ≥ 30 mL/min but \< 50 mL/min the dosage of R will be 10 mg/daily on day 1 to 21 of a 28 days course. Dexamethasone (D) (maximum period of treatment= 24 cycles) PO or IV D on days 1-2, 8-9, 15-16, 22-23. The dosage will be 20 mg between 30 minutes and 4 hours prior to K. For patients older than 75 years the dosage may be reduced at 10 mg. Carfilzomib (K) plus Lenalidomide (R) and Dexamethasone (D) Dexamethasone Carfilzomib (K) (maximum period of treatment= 24 cycles) * K on days 1-2, 8-9, 15-16 during cycles 1-12. The dosage of K will be 20 mg/m2 10' iv infusion on day 1 and 2 during cycle 1 and then 27 mg/m2 10' iv infusion thereafter; * K: on days 1-2, 15-16 during cycles 13-24. The dosage of K will be 27 mg/m2 10' iv infusion. Lenalidomide (R) (maximum period of treatment= 24 cycles) * R: 25 mg/daily on day 1 to 21 of a 28 days course; for patients with creatinine clearance ≥ 30 mL/min but \< 50 mL/min the dosage of R will be 10 mg/daily on day 1 to 21 of a 28 days course. Dexamethasone (D) (maximum period of treatment= 24 cycles) PO or IV D on days 1-2, 8-9, 15-16, 22-23. The dosage will be 20 mg between 30 minutes and 4 hours prior to K. For patients older than 75 years the dosage may be reduced at 10 mg. Carfilzomib (K) plus Lenalidomide (R) and Dexamethasone (D) Lenalidomide Carfilzomib (K) (maximum period of treatment= 24 cycles) * K on days 1-2, 8-9, 15-16 during cycles 1-12. The dosage of K will be 20 mg/m2 10' iv infusion on day 1 and 2 during cycle 1 and then 27 mg/m2 10' iv infusion thereafter; * K: on days 1-2, 15-16 during cycles 13-24. The dosage of K will be 27 mg/m2 10' iv infusion. Lenalidomide (R) (maximum period of treatment= 24 cycles) * R: 25 mg/daily on day 1 to 21 of a 28 days course; for patients with creatinine clearance ≥ 30 mL/min but \< 50 mL/min the dosage of R will be 10 mg/daily on day 1 to 21 of a 28 days course. Dexamethasone (D) (maximum period of treatment= 24 cycles) PO or IV D on days 1-2, 8-9, 15-16, 22-23. The dosage will be 20 mg between 30 minutes and 4 hours prior to K. For patients older than 75 years the dosage may be reduced at 10 mg.
- Primary Outcome Measures
Name Time Method Primary Efficacy Endpoint - 12-months overall survival The primary endpoint will be assessed 12 months after the start of treatment of the last patient. 12-month overall survival : probability of surviving from the date of beginning of therapy up to month 12 based on Kaplan-Meier estimator
- Secondary Outcome Measures
Name Time Method Secondary Endpoints 1 - ORR The endpoint will be assessed from the date of randomization to the date of the first documented progression, evaluated up to 12 months. overall response rate will be defined according to Lugano criteria. The best overall
response will be defined as the best response between the date of beginning of therapy and the last restaging. Patients without response assessment (due to whatever reason) will be considered as non-responders.Secondary Endpoints 4 - TTR through the completion of the study, an average of 1 year time to response will be defined for all patients who achieved a response (Complete Response or Partial Response) and is measured from the date of beginning of therapy until the date of response. Patients in relapse or progression will be censored at their last assessment date. Patients death due to any cause will be consider censored or competing event according to different analysis plan
Secondary Endpoints 5 - DoT through the completion of the study, an average of 1 year the duration of the treatment will be defined as the time from beginning of therapy until discontinuation due to any reason.
Secondary Endpoints 1 - CR The endpoint will be assessed from the date of randomization to the date of the first documented progression, evaluated up to 12 months. complete response rate between the date of beginning of therapy and the last restaging. Patients without response assessment (due to whatever reason) will be considered as non-responders.
Secondary Endpoints 1 - SD The endpoint will be assessed from the date of randomization to the date of the first documented progression, evaluated up to 12 months. rate between the date of beginning of therapy and the last restaging. Patients without response assessment (due to whatever reason) will be considered as non-responders.
Secondary Endpoints 3 - OS through the completion of the study, an average of 1 year overall survival will be defined as the time from beginning of therapy until death as a result of any cause; patients who are lost to follow up will be censored at their last assessment date;
Secondary Endpoints 1 - PR The endpoint will be assessed from the date of randomization to the date of the first documented progression, evaluated up to 12 months. partial response rate between the date of beginning of therapy and the last restaging. Patients without response assessment (due to whatever reason) will be considered as non-responders.
Secondary Endpoints 2 - PFS The endpoint will be assessed from the date of randomization to the date of the first documented progression, evaluated up to 12 months. progression-free survival will be defined as the time from beginning of therapy until lymphoma relapse or progression or death as a result of any cause; responding patients and patients who are lost to follow up will be censored at their last assessment date;
Trial Locations
- Locations (11)
AOU Senese - U.O.C. Ematologia
🇮🇹Siena, Italy
A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria
🇮🇹Torino, Italy
Azienda sanitaria-universitaria integrata Trieste (ASUITS) - SC Ematologia
🇮🇹Trieste, Italy
Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - SOC Clinica Ematologica
🇮🇹Udine, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia
🇮🇹Milano, Italy
ASST Spedali Civili di Brescia - Ematologia
🇮🇹Brescia, Italy
ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
🇮🇹Milano, Italy
AOU Maggiore della Carità di Novara - SCDU Ematologia
🇮🇹Novara, Italy
IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
🇮🇹Pavia, Italy
Ospedale delle Croci - Ematologia
🇮🇹Ravenna, Italy
AOU Integrata di Verona - U.O. Ematologia
🇮🇹Verona, Italy