Chronic Lymphocytic LeucemiaPhase 2NCT02320383
CLLR3: Bendamustine + GA101 (BG) in Relapsed or Refractory CLL Followed by GA101 Maintenance for Responding Patients
A Phase 2 study testing GA101 (Obinutuzumab) and Bendamustine in people with Chronic Lymphocytic Leucemia, run by Munich Municipal Hospital at 1 site in Germany.
Trial summary
A Prospective, Multicenter, Randomized Phase-Ii Trial Comparing Efficacy And Safety Of Fludarabine + Cyclophosphamide + Ga101 (Fcg) And Bendamustine + Ga101 (Bg) In Patients With Relapsed Or Refractory Cll Followed By Maintenance Therapy With Ga101 For Responding Patients Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leucemia
- What is being tested?
- GA101 (Obinutuzumab) and Bendamustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2014to Sep 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of CLL in need of treatment according to the iwCLL guidelines
- Relapsed or refractory disease after at least one, but no more than 3 prior regimens for CLL
- Medically fit patients without relevant comorbidity, defined as total CIRS score ≤6 (single score < 4 for one organ category)
- ECOG performance status of 0 - 2
- Hematology values within the following limits unless cytopenia is caused by the underlying disease, i.e. no evidence of additional bone marrow dysfunction (e.g. myelodysplastic syndrome (MDS), hypoplastic bone marrow due to toxicity of prior therapy):
- Absolute neutrophil count ≥1.5 x 109/L
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- Platelets ≥50 x 109/L and more than 7 days since last transfusion
- Creatinine clearance >60 ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured after 24 h urine collection
- Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 the institutional ULN value, unless directly attributable to the patient's CLL
- Negative serological Hepatitis B test (i.e. HBsAg negative and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative); negative testing of Hepatitis C RNA; negative HIV test within 6 weeks prior to registration
- 18 years of age or older
- Life expectancy >6 months
- Able and willing to provide written informed consent and to comply with the study protocol procedures
Who cannot join
- Detected del(17p) or TP53 mutation
- Refractoriness to FCR / BR
- Transformation of CLL to aggressive NHL (Richter's transformation)
- Known central nervous system (CNS) involvement
- Evidence of significant uncontrolled concomitant disease
- Major surgery < 30 days before screening
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- Decompensated hemolytic anemia 28 days before screening
- Hemolytic cystitis 28 days before screening
- Patients with a history of confirmed PML
- Prior treatment with GA101
- History of prior malignancy, except for conditions as listed below (a-d) and if patients have recovered from the acute side effects incurred as a result of previous therapy:
- Malignancies treated with curative intent and with no known active disease present for ≥ 2 years before registration
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease at screening
- Adequately treated cervical carcinoma in situ without evidence of disease at screening
- Surgically adequately treated low grade, early stage localized prostate cancer without evidence of disease at screening
- Use of investigational agents or concurrent anticancer treatment within the last 4 weeks before registration
- Patients with active infection requiring systemic treatment
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies and/ or known hypersensitivity to any constituent of the product
- Hypersensitivity to fludarabine, cyclophosphamide, bendamustine, GA101 and/ or to any of the excipients for example mannitol
- An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive an intensive therapy for CLL
- Legal incapacity
- Women who are pregnant or lactating
- Fertile men or women of childbearing potential unless:
- surgically sterile or ≥2 years after the onset of menopause
- willing to use a highly effective contraceptive method (Pearl Index <1) such as those listed at section 4.2.2 Exclusion criteria during study treatment and for 12 months after end of study treatment
- Vaccination with a live vaccine within a minimum of 28 days before screening
- Participation in any other clinical trial which would interfere with the study drug
- Prisoners or subjects who are institutionalized by regulatory or court order
- Persons who are in dependence to the sponsor or an investigator
Trial locations and contacts
1 site in 1 country.
About this study
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
A Prospective, Multicenter, Randomized Phase-Ii Trial Comparing Efficacy And Safety Of Fludarabine + Cyclophosphamide + Ga101 (Fcg) And Bendamustine + Ga101 (Bg) In Patients With Relapsed Or Refractory Cll Followed By Maintenance Therapy With Ga101 For Responding Patients
Read the detailed description
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.
- Conditions
- Chronic Lymphocytic Leucemia
- Being tested
- GA101 (Obinutuzumab), Bendamustine
- Keywords
- CLL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GA101 (Obinutuzumab)Biological
Also called Gazyvaro
Induction
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
Maintenance
GA101 iv 1000 mg (flat dose): every 84 days
BendamustineDrug
Also called Ribomustin, Levact
Induction
Cycle 1: d3+4 (or d2+3) - 70 mg/m² i.v., q28d
Cycle 2 - 6: d2+3 - 70 mg/m i.v., q28d
| Study group | Role | What they receive |
|---|---|---|
| B + GA101 | Experimental | Induction:
Bendamustine + GA101; a maximum of 6 cycles of BG will be administered; each cycle with a duration of 28 days
Maintenance:
GA101 i.v. 1000 mg (flat dose): every 84 days starting on final restaging continued until progression or to a maximum of 2 years Receives: Biological: GA101 (Obinutuzumab); Drug: Bendamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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).
Measured: The response to the induction phase will be performed 84 days after first dose of last cycle of induction administered
Secondary outcomes (9)
MRD levels
MRD levels (evaluation of minimal residual disease (MRD)) by flow cytometry during treatment and maintenance
Measured: 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
Progression free survival (PFS)
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.
Measured: 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
Event-free survival (EFS)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
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.
Measured: The response to the induction phase will be performed 84 days after first dose of last cycle of induction administered
Complete response rate
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).
Measured: The response to the induction phase will be performed 84 days after first dose of last cycle of induction administered
Safety parameters during induction and maintenance phase
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2014 (estimated)
- Study startNov 2014
- Primary completionDec 2017
- Study completionSep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeucemiaStudies 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
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Munich Municipal Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- German CLL Study Group
- Responsible party
- Sponsor
- Investigators
- Clemens-Martin Wendtner, Prof. Dr., Principal investigator, Klinikum München GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02320383
- Sponsor's protocol ID
- CLLR3
- Status last verified
- Aug 2018
- First submitted
- 1 Sep 2014
- Last updated
- 13 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02320383
- Acronym / sponsor ID
- CLLR3
- Conditions
- Chronic Lymphocytic Leucemia
- Keywords
- CLL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Munich Municipal HospitalUniversity, hospital or other
- Collaborators
- German CLL Study Group
- Study start
- Nov 2014 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Sep 2022 (estimated)
- First posted
- 19 Dec 2014 (estimated)
- 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.
A Prospective, Multicenter, Randomized Phase-Ii Trial Comparing Efficacy And Safety Of Fludarabine + Cyclophosphamide + Ga101 (Fcg) And Bendamustine + Ga101 (Bg) In Patients With Relapsed Or Refractory Cll Followed By Maintenance Therapy With Ga101 For Responding Patients
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| B + GA101 | Experimental | Biological: GA101 (Obinutuzumab), Drug: BendamustineInduction: Bendamustine + GA101; a maximum of 6 cycles of BG will be administered; each cycle with a duration of 28 days Maintenance: GA101 i.v. 1000 mg (flat dose): every 84 days starting on final restaging continued until progression or to a maximum of 2 years |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Diagnosis of CLL in need of treatment according to the iwCLL guidelines
- Relapsed or refractory disease after at least one, but no more than 3 prior regimens for CLL
- Medically fit patients without relevant comorbidity, defined as total CIRS score ≤6 (single score < 4 for one organ category)
- ECOG performance status of 0 - 2
- Hematology values within the following limits unless cytopenia is caused by the underlying disease, i.e. no evidence of additional bone marrow dysfunction (e.g. myelodysplastic syndrome (MDS), hypoplastic bone marrow due to toxicity of prior therapy):
Key exclusion criteria (29 listed)
- Detected del(17p) or TP53 mutation
- Refractoriness to FCR / BR
- Transformation of CLL to aggressive NHL (Richter's transformation)
- Known central nervous system (CNS) involvement
- Evidence of significant uncontrolled concomitant disease
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 |
|---|---|---|
| GA101 (Obinutuzumab)Also: GazyvaroInduction 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 Maintenance GA101 iv 1000 mg (flat dose): every 84 days | Biological | B + GA101 |
| BendamustineAlso: Ribomustin, LevactInduction Cycle 1: d3+4 (or d2+3) - 70 mg/m² i.v., q28d Cycle 2 - 6: d2+3 - 70 mg/m i.v., q28d | Drug | B + GA101 |
Primary outcome
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).
9 secondary outcomes
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
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
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
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2018.
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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.
Clemens-Martin Wendtner, Prof. Dr. principal investigator
Klinikum München GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GA101 (Obinutuzumab) and Bendamustine in people with Chronic Lymphocytic Leucemia, run by Munich Municipal Hospital at 1 site in Germany.
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 13 inclusion and 29 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 13 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Aug 2018.