Ignite Creation Date:
2025-12-25 @ 12:04 AM
Ignite Modification Date:
2026-02-11 @ 9:10 PM
Study NCT ID:
NCT02356458
Status:
TERMINATED
Last Update Posted:
2022-03-11
First Post:
2015-02-02
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Combination of Ibrutinib and Bortezomib to Treat Patients With Mantle Cell Lymphoma
Sponsor:
Swiss Cancer Institute
Organization:
Study Overview
Official Title:
Combination of Ibrutinib and Bortezomib Followed by Ibrutinib Maintenance to Treat Patients With Relapsed and Refractory Mantle Cell Lymphoma; a Multicenter Phase I/II Trial.
Status:
TERMINATED
Status Verified Date:
2022-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
SAKK Board decision of 14th November 2020 due to financial reasons.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Mantle cell lymphoma (MCL) remains an incurable disease with frequent relapses and no standard therapeutic options in case of relapse. Prolongation of remissions or induction of longer remissions is therefore crucial. Recently, a synergistic increase in the proteasomal inhibition of ibrutinib in both bortezomib-sensitive and refractory MCL cells was shown. These findings, along with the reported single agent activities of both drugs and the non-overlapping toxicities, are the rationale to combine ibrutinib and bortezomib in MCL in this trial
Detailed Description:
Disease background, therapy background and aim
Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma. It represents \~5% of all lymphomas and typically is present in advanced stages, a median age of 60-65 years and a dismal prognosis with a median survival of \~3 years. Currently, it remains incurable, as the patients will relapse after first line treatment and require subsequent therapy. The disease-free survival is progressively shorter with each subsequent relapse.
Currently, there is no standard therapy for relapsed MCL patients. MCL is predominantly a disease of the elderly who are not suitable for aggressive chemotherapy. Allogeneic transplants are preferred in young and fit patients, whereas (preferably single agent) chemotherapy is used to treat older patients, but usually with short duration of responses. Recently, the therapeutic armamentarium has been expanded with the availability of novel agents targeting crucial and deregulated pathways in MCL. These include the Bruton's Kinase (BTK) inhibitor ibrutinib with excellent single agent activities. New therapeutic options in the targeted patient population are clearly needed to prolong remissions especially for elderly patients where aggressive chemotherapy and allogeneic transplants are no suitable treatment options. Recently, a synergistic increase in the proteasomal inhibition of ibrutinib in both bortezomib-sensitive and refractory MCL cells was shown.
This trial is targeting patients with diagnosis of refractory or relapsed MCL disease after pretreatment with ≤2 lines of non-bortezomib-containing chemotherapy. The proposed treatment of ibrutinib in combination with bortezomib might lead to an improvement of the therapy in the targeted relapsed/refractory patient population. Given the absence of a dose-limiting toxicity also when applied long-term, ibrutinib is well suited in this patient population as a maintenance therapy. Therefore, the combination treatment of the trial is followed by a maintenance therapy part for patients that had no disease progression. New treatment options should control the disease as best and long as possible.
Treatment
Treatment consists of 6 cycles of 21 days each of ibrutinib in combination with bortezomib, followed by a maintenance therapy with ibrutinib monotherapy. In the maintenance therapy courses repeat every 28-days in the absence of disease progression or unacceptable toxicity.
Objectives Phase I The primary object of the trial is to establish the recommended phase II dose (RP2D) of ibrutinib in combination with bortezomib in patients with relapsed or refractory MCL.
The secondary objectives are
* to determine the safety and tolerability of ibrutinib in combination with bortezomib and
* to assess the preliminary antitumor activity of ibrutinib in combination with bortezomib Phase II The main object of the trial is to define the efficacy of the combination treatment of ibrutinib with bortezomib in patients with relapsed or refractory MCL.
The secondary objectives are
* to determine the safety and tolerability of the RP2D and
* to assess the efficacy of ibrutinib in combination with bortezomib in patients with relapsed MCL followed by an ibrutinib maintenance therapy.
Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma. It represents \~5% of all lymphomas and typically is present in advanced stages, a median age of 60-65 years and a dismal prognosis with a median survival of \~3 years. Currently, it remains incurable, as the patients will relapse after first line treatment and require subsequent therapy. The disease-free survival is progressively shorter with each subsequent relapse.
Currently, there is no standard therapy for relapsed MCL patients. MCL is predominantly a disease of the elderly who are not suitable for aggressive chemotherapy. Allogeneic transplants are preferred in young and fit patients, whereas (preferably single agent) chemotherapy is used to treat older patients, but usually with short duration of responses. Recently, the therapeutic armamentarium has been expanded with the availability of novel agents targeting crucial and deregulated pathways in MCL. These include the Bruton's Kinase (BTK) inhibitor ibrutinib with excellent single agent activities. New therapeutic options in the targeted patient population are clearly needed to prolong remissions especially for elderly patients where aggressive chemotherapy and allogeneic transplants are no suitable treatment options. Recently, a synergistic increase in the proteasomal inhibition of ibrutinib in both bortezomib-sensitive and refractory MCL cells was shown.
This trial is targeting patients with diagnosis of refractory or relapsed MCL disease after pretreatment with ≤2 lines of non-bortezomib-containing chemotherapy. The proposed treatment of ibrutinib in combination with bortezomib might lead to an improvement of the therapy in the targeted relapsed/refractory patient population. Given the absence of a dose-limiting toxicity also when applied long-term, ibrutinib is well suited in this patient population as a maintenance therapy. Therefore, the combination treatment of the trial is followed by a maintenance therapy part for patients that had no disease progression. New treatment options should control the disease as best and long as possible.
Treatment
Treatment consists of 6 cycles of 21 days each of ibrutinib in combination with bortezomib, followed by a maintenance therapy with ibrutinib monotherapy. In the maintenance therapy courses repeat every 28-days in the absence of disease progression or unacceptable toxicity.
Objectives Phase I The primary object of the trial is to establish the recommended phase II dose (RP2D) of ibrutinib in combination with bortezomib in patients with relapsed or refractory MCL.
The secondary objectives are
* to determine the safety and tolerability of ibrutinib in combination with bortezomib and
* to assess the preliminary antitumor activity of ibrutinib in combination with bortezomib Phase II The main object of the trial is to define the efficacy of the combination treatment of ibrutinib with bortezomib in patients with relapsed or refractory MCL.
The secondary objectives are
* to determine the safety and tolerability of the RP2D and
* to assess the efficacy of ibrutinib in combination with bortezomib in patients with relapsed MCL followed by an ibrutinib maintenance therapy.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: