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

NCT03891355 | Unknown Phase 2 DMC

• 1 other identifier: FIL_KLIMT
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 11

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.

Conditions

Mantle Cell Lymphoma

Keywords

Carfilzomib; Lenalidomide; Dexamethasone; relapsed-refractory or intolerant mantle cell lymphomas

Outcome Measures

Primary Outcomes (1)

• Primary Efficacy Endpoint - 12-months overall survival

  12-month overall survival : probability of surviving from the date of beginning of therapy up to month 12 based on Kaplan-Meier estimator

  The primary endpoint will be assessed 12 months after the start of treatment of the last patient.

Secondary Outcomes (8)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib

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

Lenalidomide DRUG

Lenalidomide

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

Dexamethasone DRUG

Dexamethasone

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

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (11)

ASST Spedali Civili di Brescia - Ematologia

Brescia, 25123, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia

Milan, 20133, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

Milan, 20162, Italy

Location

AOU Maggiore della Carità di Novara - SCDU Ematologia

Novara, 28100, Italy

Location

IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia

Pavia, 27100, Italy

Location

Ospedale delle Croci - Ematologia

Ravenna, 48121, Italy

Location

AOU Senese - U.O.C. Ematologia

Siena, 53100, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria

Torino, 10126, Italy

Location

Azienda sanitaria-universitaria integrata Trieste (ASUITS) - SC Ematologia

Trieste, 34121, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - SOC Clinica Ematologica

Udine, 33100, Italy

Location

AOU Integrata di Verona - U.O. Ematologia

Verona, 37134, Italy

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

carfilzomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Francesco Zaja, Prof.

  Ospedale Maggiore Azienda Sanitaria Universitaria Trieste Ematologia

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: 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. After checking inclusion and exclusion criteria and signing written informed consent, the patient will be enrolled with an identification numeric code.

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: March 27, 2019
• Study Start: September 30, 2019
• Primary Completion: December 4, 2020
• Study Completion: December 8, 2022
• Last Updated: September 15, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (11)