Copanlisib in Combination With Venetoclax in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma.
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|ClinicalTrials.gov Identifier: NCT03886649|
Recruitment Status : Recruiting
First Posted : March 22, 2019
Last Update Posted : July 3, 2019
A significant number of patients with non-Hodgkin lymphoma (NHL) are not cured with available treatments and will eventually relapse. Those patients might not be able to tolerate more bone marrow toxicity, limiting their treatment options. Preclinical in vitro studies have demonstrated a synergism of venetoclax and copanlisib in different lymphomas. This may represent a safe and effective therapy for patients who relapsed or did not respond to standard therapy.
The primary objective of this phase I trial is to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of copanlisib in combination with venetoclax in patients with relapsed or refractory B-cell NHL.
|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkin Lymphoma||Drug: Copanlisib Drug: Venetoclax||Phase 1|
There are many different types of NHL. A lot of progress has been made over the last years in the management of NHL, and while some can be cured with available treatments, for others new treatments are necessary. A significant number of patients that cannot be cured with the available treatments will eventually relapse.
Dysregulation of apoptosis via overexpression of the antiapoptotic BCL-2 protein is paramount for several subtypes of NHL. On the other hand, PI3K is a central pathway in the pathogenesis of lymphoma, and PI3K signaling is critical for the proliferation and survival of malignant cells such as follicular lymphoma (FL), marginal zone lymphoma (MZL), and others.
The combination of copanlisib (PI3K inhibitor) and venetoclax (BLC-2 inhibitor) is interesting given their known single agent activity in B-cell NHL and their synergy observed in B-cell NHL preclinical models. The pharmacologic inhibition of PI3K by copanlisib has translated into significant clinical activity in different lymphoma subtypes. Venetoclax has proven successful in CLL and the first results in NHL are encouraging. Both compounds are currently in other combination studies in SLL/CLL and NHL but there are currently no clinical trials studying this particular combination.
There is a need to further improve approaches in the relapsed/refractory setting of patients with NHL in need of systemic therapy and this combination may provide an opportunity for an active and well-tolerated regimen that does not present the short and long-term toxicities of chemotherapy.
The phase Ib study here proposed will evaluate the safety, tolerability and preliminary antitumor activity of the novel combination of copanlisib with venetoclax, two drugs with single agent activity across different lymphoma subtypes in the dose escalation and in two small cohorts of patients with FL and MZL in the expansion phase.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||In the dose escalation phase, relapsed/refractory B-cell NHL patients are included. In the dose expansion phase, patients with MZL (Marginal zone lymphoma) and FL (Follicular lymphoma) will be treated.|
|Masking:||None (Open Label)|
|Official Title:||Copanlisib in Combination With Venetoclax in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma. A Multicenter Phase Ib Trial With Two Expansion Cohorts|
|Estimated Study Start Date :||July 2019|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2022|
Experimental: Copanlisib + Venetoclax
Phase Ib -> dose escalation with 2 expansion cohorts
Duration of IMP administration: a maximum of twelve 28-day cycles of the combination treatment. Copanlisib will be administered i.v. on days 1, 8, and 15 of each cycle. The only dose level 1 (DL1) is 60 mg copanlisib.
Duration of IMP administration: a maximum of twelve 28-day cycles of the combination treatment. Copanlisib will be administered i.v. on days 1, 8, and 15 of each cycle. The starting dose is dose level 1 (DL1): 600 mg venetoclax.
- Dose-limiting toxicities (DLTs) during the first cycle of treatment [ Time Frame: day 28 of the first cycle ]
Dose-limiting toxicity (DLT) is defined as any of the adverse events (AEs) which:
- occurs during cycle 1 of the trial treatment (defined as the DLT monitoring period), and
- is considered by the investigator or the sponsor to be at least possibly related to at least one of the drugs given in the combination trial treatment venetoclax+copanlisib.
- Adverse events (AEs) [ Time Frame: at 12 months ]
- Complete response (CR) at 6 months and 12 months [ Time Frame: at 6 months and 12 months ]
- Overall response (OR) at 6 months and 12 months [ Time Frame: at 6 months and 12 months ]
- OR based on best response [ Time Frame: at 12 months ]
- Progression-free survival (PFS) at 12 months [ Time Frame: at 12 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03886649
|Contact: Lena Sokol, PhD||+41 31 389 91 email@example.com|
|Basel, Switzerland, 4031|
|Contact: Fatime Krasniqi, MD +41 61 265 5059 KrasniqiF@uhbs.ch|
|Principal Investigator: Fatime Krasniqi, MD|
|Istituto Oncologico della Svizzera Italiana||Recruiting|
|Bellinzona, Switzerland, 6500|
|Contact: Anastasios Stathis, MD +41 91 811 89 31 firstname.lastname@example.org|
|Principal Investigator: Anastasios Stathis, MD|
|Bern, Switzerland, CH-3010|
|Contact: Urban Novak, MD +41 31 632 19 92 email@example.com|
|Principal Investigator: Urban Novak, MD|
|Hôpitaux Universitaires de Genève||Recruiting|
|Genève, Switzerland, 1211|
|Contact: Alex Friedlaender, MD +41 22 372 29 01 firstname.lastname@example.org|
|Principal Investigator: Alex Friedlaender, MD|
|Kantonsspital St. Gallen||Recruiting|
|St. Gallen, Switzerland, 9007|
|Contact: Dagmar Hess, MD +41 71 494 11 11 email@example.com|
|Principal Investigator: Dagmar Hess, MD|
|Zürich, Switzerland, 8091|
|Contact: Thorsten Zenz, Prof +41 44 255 94 96 firstname.lastname@example.org|
|Principal Investigator: Thorsten Zenz, Prof|
|Study Chair:||Anastasios Stathis, MD||IOSI, Ospedale San Giovanni, Bellinzona|
|Study Chair:||Emanuele Zucca||IOSI, Ospedale San Giovanni, Bellinzona|