Carfilzomib + Lenalidomide and Dexamethasone for BTK Inhibitors Relapsed-refractory or Intolerant MCL

NCT ID: NCT03891355

Last Updated: 2022-09-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-30
• Study Completion Date: 2022-12-08

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.

Conditions

Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carfilzomib (K) plus Lenalidomide (R) and Dexamethasone (D)

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.

Group Type: EXPERIMENTAL

Carfilzomib

Intervention Type: DRUG

Carfilzomib

Lenalidomide

Intervention Type: DRUG

Lenalidomide

Dexamethasone

Intervention Type: DRUG

Dexamethasone

Interventions

Carfilzomib

Carfilzomib

Intervention Type: DRUG

Lenalidomide

Lenalidomide

Intervention Type: DRUG

Dexamethasone

Dexamethasone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Previous treatment with BTKi monotherapy or BTKi containing regimens with R/R disease; and/or patients who discontinued BTKi monotherapy or BTKi containing regimens for adverse events and have active disease necessitating treatment;
• Previous treatment with Lenalidomide is accepted if patient resulted responsive and interrupted Lenalidomide at least 12 months before enrollment to this study;
• Patient age is ≥ 18 < 80 years;
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2;
• Understands and voluntarily signs an informed consent form;
• Able to adhere to the study visit schedule and other protocol requirements; Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan cannot be performed). Note: Patients with bone marrow involvement are eligible;
• Adequate hematological counts: ANC > 1.5 x 109/L and platelet count > 75 x 109/L unless due to bone marrow involvement by MCL;
• Conjugated bilirubin up to 2 x ULN unless due to liver involvement by MCL;
• Alkaline phosphatase and transaminases up to 2 x ULN unless due to liver involvement by MCL;
• Creatinine clearance ≥ 30 ml/min; a dose reduction of Lenalidomide for patients with creatinine clearance ≥ 30 mL/min but < 50 mL/min is planned;
• Patient has the ability to swallow capsules or tablets;
• Life expectancy ≥ 2 months;
• Male and Female patients: accordance to comply with Lenalidomide Risk Management Plan for pregnancy prevention.

Exclusion Criteria

• Patient who have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study;
• Patient has a history of CNS involvement with lymphoma;
• Patient with previous history of malignancies (apart MCL) ≤ 3 years before study accrual with the exception of currently treated basal cell and squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix;
• History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances;
• Patient has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, uncontrolled hypertension, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), active hemorrhage, psychiatric illness, active or uncontrolled infection that in the investigator opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form;
• Creatinine clearance < 30 ml/min;
• Significant neuropathy (Grades 3 - 4, or Grade 2 with pain) within 14 days prior to enrollment;
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize Carfilzomib);
• Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to hydration due to preexisting pulmonary or cardiac impairment;
• Patients with LVEF <40%
• Patients with New York Health Association (NYHA) Class III and IV heart failure; myocardial infarction in the preceding 6 months; conduction abnormalities, including but not limited to atrial fibrillation, atrioventricular (AV) block, QT prolongation, sick sinus syndrome, ventricular tachycardia;
• Patients with severe bradycardia (heart rate <40 bpm, hypotension, light-headedness, syncope);
• Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment;
• Patients with active pulmonary embolism or deep vein thrombosis (diagnosed within 30 days of study enrollment);
• Patient has a known history of HIV seropositivity;
• Patient has active HBV hepatitis. The following categories of HBV positive patients but with no evidence of active hepatitis may be considered for the study:

• patient is HBsAg + with HBV DNA < 2000 UI/ml (inactive carriers); HBV DNA > 2000 UI/ml is criteria of exclusion;
• patient is HBsAg - HBsAb +;
• patient is HBsAg - but HBcAb +
• Patient with HCV active hepatitis are excluded from the study. Patient with no evidence of active hepatitis and/or advanced chronic liver disease according to liver biopsy or fibro-scan evaluation may be included into the study;
• Previous treatment with Lenalidomide if patient resulted primary refractory to Lenalidomide or interrupted Lenalidomide less than 12 months before enrollment to this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco Zaja, Prof.

Role: PRINCIPAL_INVESTIGATOR

Ospedale Maggiore Azienda Sanitaria Universitaria Trieste Ematologia

Locations

ASST Spedali Civili di Brescia - Ematologia

Brescia, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia

Milan, , Italy

ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

Milan, , 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 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

AOU Integrata di Verona - U.O. Ematologia

Verona, , Italy

Countries

Italy

Other Identifiers

FIL_KLIMT

Identifier Type: -

Identifier Source: org_study_id