Mantle Cell LymphomaPhase 2FIL_KLIMTNCT03891355

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

A Phase 2 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Mantle Cell Lymphoma, run by Fondazione Italiana Linfomi - ETS at 11 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Mantle Cell Lymphoma
What is being tested?: Carfilzomib, Lenalidomide and Dexamethasone
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 11 sitesItaly
Study dates: 30 Sep 2019to 8 Dec 2022
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

None listed.

Who cannot join

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;

Show all 21Show fewer

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.

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

Italy11 sites

ASST Spedali Civili di Brescia - Ematologia
Brescia, 25123
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia
Milan, 20133
ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
Milan, 20162
AOU Maggiore della Carità di Novara - SCDU Ematologia
Novara, 28100
IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
Pavia, 27100
Ospedale delle Croci - Ematologia
Ravenna, 48121
AOU Senese - U.O.C. Ematologia
Siena, 53100
A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria
Torino, 10126
Azienda sanitaria-universitaria integrata Trieste (ASUITS) - SC Ematologia
Trieste, 34121
Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - SOC Clinica Ematologica
Udine, 33100
AOU Integrata di Verona - U.O. Ematologia
Verona, 37134

Other trials in Italy

About this study

Official title: Carfilzomib (K) Plus Lenalidomide (R) and Dexamethasone (D) for BTK Inhibitors Relapsed-refractory or Intolerant Mantle Cell Lymphomas: a Phase II Study

Read the 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
Being tested: Carfilzomib, Lenalidomide, Dexamethasone
Keywords: Carfilzomib, Lenalidomide, Dexamethasone, relapsed-refractory or intolerant mantle cell lymphomas
Medical subject headings: Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CarfilzomibDrug
Carfilzomib
LenalidomideDrug
Lenalidomide
DexamethasoneDrug
Dexamethasone

Study groups in NCT03891355
Study group	Role	What they receive
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. Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (8)

Secondary Endpoints 1 - ORR
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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;
Measured: 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 3 - OS
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;
Measured: through the completion of the study, an average of 1 year
Secondary Endpoints 4 - TTR
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
Measured: through the completion of the study, an average of 1 year
Secondary Endpoints 5 - DoT
the duration of the treatment will be defined as the time from beginning of therapy until discontinuation due to any reason.
Measured: through the completion of the study, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Sep 20198 Dec 2022

First posted27 Mar 2019
Study start30 Sep 2019
Primary completion4 Dec 2020
Study completion8 Dec 2022 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model 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. After checking inclusion and exclusion criteria and signing written informed consent, the patient will be enrolled with an identification numeric code.
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03891355
Sponsor's protocol ID: FIL_KLIMT
Acronym: FIL_KLIMT
Status last verified: Sep 2022
First submitted: 15 Mar 2019
Last updated: 15 Sep 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
RecruitingPhase 3
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Lymphoma
RecruitingPhase 1
A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )
Lymphoma, Non-Hodgkin, B-cell Lymphoma
RecruitingPhase 2
Auto Stem Cell Transplant for Lymphoma Patients
Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer

All Mantle Cell Lymphoma trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Carfilzomib (K) Plus Lenalidomide (R) and Dexamethasone (D) for BTK Inhibitors Relapsed-refractory or Intolerant Mantle Cell Lymphomas: a Phase II Study
ClinicalTrials.gov ID: NCT03891355
Acronym / sponsor ID: FIL_KLIMT / FIL_KLIMT
Conditions: Mantle Cell Lymphoma
Keywords: Carfilzomib, Lenalidomide, Dexamethasone, relapsed-refractory or intolerant mantle cell lymphomas
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 16 participants (actual)
Lead sponsor: Fondazione Italiana Linfomi - ETSUniversity, hospital or other
Study start: 30 Sep 2019 (actual)
Primary completion: 4 Dec 2020 (actual)
Study completion: 8 Dec 2022 (estimated)
First posted: 27 Mar 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model 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. After checking inclusion and exclusion criteria and signing written informed consent, the patient will be enrolled with an identification numeric code.

Arm	Type	Receives
Carfilzomib (K) plus Lenalidomide (R) and Dexamethasone (D)	Experimental	Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneCarfilzomib (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.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (0 listed)

Key exclusion criteria (21 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CarfilzomibCarfilzomib	Drug	Carfilzomib (K) plus Lenalidomide (R) and Dexamethasone (D)
LenalidomideLenalidomide	Drug	Carfilzomib (K) plus Lenalidomide (R) and Dexamethasone (D)
DexamethasoneDexamethasone	Drug	Carfilzomib (K) plus Lenalidomide (R) and Dexamethasone (D)

Primary outcome

Primary Efficacy Endpoint - 12-months overall survival
Time frame: 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

8 secondary outcomes

Secondary Endpoints 1 - ORR
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 3 - OS
Time frame: through the completion of the study, an average of 1 year
Secondary Endpoints 4 - TTR
Time frame: through the completion of the study, an average of 1 year
Secondary Endpoints 5 - DoT
Time frame: through the completion of the study, an average of 1 year

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2022.
Individual participant dataSharing planned: No

Related trials for Mantle Cell Lymphoma

Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
RecruitingPhase 3
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Lymphoma
RecruitingPhase 1
A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )
Lymphoma, Non-Hodgkin, B-cell Lymphoma
RecruitingPhase 2
Auto Stem Cell Transplant for Lymphoma Patients
Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Francesco Zaja, Prof. principal investigator

Ospedale Maggiore Azienda Sanitaria Universitaria Trieste Ematologia

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Mantle Cell Lymphoma, run by Fondazione Italiana Linfomi - ETS at 11 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 15 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Efficacy Endpoint - 12-months overall survival (time frame: The primary endpoint will be assessed 12 months after the start of treatment of the last patient.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03891355.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2022.