CLLR3: Bendamustine + GA101 (BG) in Relapsed or Refractory CLL Followed by GA101 Maintenance for Responding Patients
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|ClinicalTrials.gov Identifier: NCT02320383|
Recruitment Status : Active, not recruiting
First Posted : December 19, 2014
Last Update Posted : August 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leucemia||Biological: GA101 (Obinutuzumab) Drug: Bendamustine||Phase 2|
The type II anti-CD20 antibody GA101 has demonstrated a high efficacy as single agent (ORR 62%) and was well tolerated in previously treated patients with CLL.
Additionally, there is evidence that immunochemotherapy consisting of fludarabine, cyclophosphamide and rituximab (FCR) is active in patients with refractory and relapsed CLL.
Besides FCR, the combination of bendamustine with rituximab (BR) has shown to be active in both relapsed and previously untreated patients with CLL.
In preclinical studies GA101, a glycoengineered, humanized type II anti-CD20 antibody, has shown superior activity compared with type I antibodies.
Therefore, a combination therapy with FC + GA101 (FCG) or B + GA101 (BG) might further improve the therapeutic outcome in relapsed or refractory CLL. The CLLR3 trial was designed to investigate and to compare the efficacy and safety of induction with both immunochemotherapies followed additionally by a maintenance therapy with GA101 for responding patients.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Prospective, Multicenter, Phase-II Trial Evaluating Efficacy and Safety of Bendamustine + GA101 (BG) in Patients With Relapsed CLL Followed by Maintenance Therapy With GA101 for Responding Patients|
|Actual Study Start Date :||November 2014|
|Actual Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||September 2022|
Experimental: B + GA101
Bendamustine + GA101; a maximum of 6 cycles of BG will be administered; each cycle with a duration of 28 days
GA101 i.v. 1000 mg (flat dose): every 84 days starting on final restaging continued until progression or to a maximum of 2 years
Biological: GA101 (Obinutuzumab)
Cycle 1: d1 - 100 mg, (d1 or) d2 - 900 mg, d8+15 - 1000 mg i.v., q28d
Cycle 2 - 6: d1 - 1000 mg i.v., q28d
GA101 iv 1000 mg (flat dose): every 84 days
Other Name: Gazyvaro
Cycle 1: d3+4 (or d2+3) - 70 mg/m² i.v., q28d
Cycle 2 - 6: d2+3 - 70 mg/m i.v., q28d
- Evaluate the efficacy of two regimens of immunochemotherapy, i.e. Response rates of Fludarabine, Cyclophosphamide plus GA101 (FCG) and Bendamustine plus GA101 (BG), in patients with relapsed or refractory CLL. [ Time Frame: The response to the induction phase will be performed 84 days after first dose of last cycle of induction administered ]Efficacy of FCG and/ or BG is confirmed if the ORR is at least 80% (response rate of an active regimen) respectively and is assessed to be not effective if the ORR is 60% or less (ORR of an uninteresting regimen).
- MRD levels [ Time Frame: MRD levels will be assessed at 84 days after first dose of last cycle of induction and during maintenance every 3 months up to 2 years for responding patients ]MRD levels (evaluation of minimal residual disease (MRD)) by flow cytometry during treatment and maintenance
- Progression free survival (PFS) [ Time Frame: The time to disease progression will be measured from the date of randomization to the date of first disease progression, assessed up to 54 months ]From the date of randomization to the date of first disease progression (as defined by the iwCLL response criteria) or death by any cause, whichever occurs first.
- Event-free survival (EFS) [ Time Frame: From the date of randomization to the date of first disease progression, start of next CLL treatment or death by any cause, whichever occurs first, assessed up to 54 months ]
- Overall survival (OS) [ Time Frame: Overall survival (OS) will be calculated from the date of randomization to the date of death due to any cause, assessed up to 54 months ]
- Duration of response in patients with CR/ CRi, clinical CR / clinical CRi or nPR/ PR [ Time Frame: This will be measured from the date of first documentation of response to the date of first disease progression, or death by any cause, whichever occurs first, assessed up to 54 months ]
- Time to next anti-leukemia treatment [ Time Frame: From time of randomization to the date of initiation of next treatment for CLL or death by any cause, whichever occurs first, assessed up to 54 months ]
- Overall response rate in biological defined risk groups [ Time Frame: The response to the induction phase will be performed 84 days after first dose of last cycle of induction administered ]Is defined by the proportion of patients having achieved a CR/ CRi, clinical CR/ CRi or nPR/ PR as best response based on the respective population.
- Complete response rate [ Time Frame: The response to the induction phase will be performed 84 days after first dose of last cycle of induction administered ]Is defined by the proportion of patients having achieved a CR/ CRi as best response based on the respective population (= number of patients with best response CR/ CRi divided by the number of the respective population).
- Safety parameters during induction and maintenance phase [ Time Frame: SAE: until end of study, AE: From day 1 of the first cycle until 28 days after the end of the treatment, assessed up to 54 months ]During induction and maintenance phase until End of Study. Safety parameters: type, frequency, and severity of adverse events (AEs) and relationship of AEs to study treatment. Furthermore the safety profile including second malignancies of patients treated with FCG/ BG induction treatment and patients with and without maintenance will be evaluated and compared descriptively.
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): NCT02320383
|German CLL Study Group|
|Cologne, Germany, 50923|
|Principal Investigator:||Clemens-Martin Wendtner, Prof. Dr.||Klinikum München GmbH|