Chronic Lymphocytic LeucemiaPhase 2NCT02445131
Sequential Regimen of Bendamustine-Debulking Followed by CAL-101 and GA101-Induction and -Maintenance in CLL (CLL2-BCG)
A Phase 2 study testing Bendamustine, GA101 and CAL-101 in people with Chronic Lymphocytic Leucemia, run by German CLL Study Group at 1 site in Germany.
Trial summary
The CLL2-BCG-trial is a prospective, open-label, multicenter phase-II-trial to evaluate the efficacy and safety of a sequential regimen of a debulking with bendamustine followed by an induction with GA101 (obinutuzumab) and CAL-101 (idelalisib) followed by CAL-101 and GA101-maintenance in CLL 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?
- Bendamustine, GA101 and CAL-101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteGermany
- Study dates
- 28 May 2015to 9 Mar 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
- documented chronic lymphocytic leukemia (CLL) requiring treatment according to International Working Group on CLL (iwCLL) criteria
- adequate hematologic function: platelets ≥ 25.000/µl, neutrophils ≥ 1.000/µl and hemoglobin ≥8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
- adequate renal function: a creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection
- adequate liver function: total bilirubin ≤1,5x, aspartate aminotransferase (AST) / alanin aminotransferase (ALT) ≤2.5x the institutional upper limit of normal (ULN) value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
- negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
- age ≥ 18 years
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- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2, ECOG 3 is only permitted if related to CLL
- life expectancy ≥ 6 months
- ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
Who cannot join
- transformation of CLL (i.e. Richter's transformation, prolymphocytic leukemia)
- known central nervous system (CNS) involvement
- confirmed progressive multifocal leukoencephalopathy (PML)
- malignancies other than CLL currently requiring systemic therapies
- uncontrolled infection requiring systemic treatment
- any comorbidity or organ system impairment rated with a cumulative illness rating scale (CIRS) score of 4, excluding the eyes/ears/nose/throat/larynx organ system or any other life-threatening illness, medical condition or organ system dysfunction that - in the investigator´s opinion - could compromise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastrointestinal tract)
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- ongoing inflammatory bowel disease
- ongoing drug induced pneumonitis
- use of investigational agents which would interfere with the study drug ≤28 days prior to registration
- known hypersensitivity to GA101 (obinutuzumab), CAL-101 (idelalisib) or any of the excipients
- pregnant women and nursing mothers
- fertile men or women of childbearing potential unless surgically sterile or ≥ 2 years after the onset of menopause, or willing to use two methods of reliable contraception including one highly effective (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after end of study treatment
- vaccination with a live vaccine ≤28 days prior to registration
- legal incapacity
- 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: Prospective, Open-label, Multicenter Phase-II Trial to Evaluate Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by GA101 (Obinutuzumab) and CAL-101 (Idelalisib) Followed by CAL-101 and GA101 Maintenance in CLL Patients
The CLL2-BCG-trial is a prospective, open-label, multicenter phase-II-trial to evaluate the efficacy and safety of a sequential regimen of a debulking with bendamustine followed by an induction with GA101 (obinutuzumab) and CAL-101 (idelalisib) followed by CAL-101 and GA101-maintenance in CLL patients
Read the detailed description
In the CLL2-BCG-trial, a total of 62 patients of an allcomer CLL population (irrespective of physical fitness, previous therapies and prognostic factors) with an indication for treatment will be included. Patients will receive 2 cycles of debulking treatment with bendamustine unless contraindications (e.g. refractoriness) are present or a debulking is not indicated due to a low tumor burden. Afterwards, 6 cycles of induction treatment with GA101 (obinutuzumab, 3 doses in the first cycle and monthly in cycles 2-6) and CAL-101 (idelalisib, continuously starting in cycle 2) will be applied. The primary endpoint overall response rate will be assessed at final restaging (2 months after end of induction treatment). Patients benefitting from treatment receive further therapy with GA101 (3 monthly) and CAL-101 (continuously) in a maintenance phase for up to 24 months. Maintenance treatment will be stopped in case of achievement of a complete remission and confirmation of MRD (minimal residual disease) negativity in peripheral blood or if unacceptable toxicity or progression occurs.
- Conditions
- Chronic Lymphocytic Leucemia
- Being tested
- Bendamustine, GA101, CAL-101
- Keywords
- CLL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustineDrug
Debulking: Cycles 1 - 2, d1 \& 2: 70 mg/m2 i.v.
GA101Drug
Also called Obinutuzumab
Induction: Cycle 1: d1: 100mg, d1(or2): 900mg, d8 \& 15: 1000mg; Cycle 2-6: d1: 1000mg
Maintenance: Cycle 1-8 (Duration 12 weeks): d1 1000 mg.
CAL-101Drug
Also called Idelalisib
Induction: Cycle 2-6: d1-28: 150 mg p.o.
Maintenance: Cycles 1-8 (Duration 12 weeks): d1-84 150 mg p.o.
| Study group | Role | What they receive |
|---|---|---|
| Bendamustine + GA101 + CAL-101 | Experimental | Bendamustine: 70 mg/m2 i.v. GA101: 1000 mg CAL-101: 150 mg p.o. Receives: Drug: Bendamustine; Drug: GA101; Drug: CAL-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
Proportion of patients responding according to international working Group on chronic lymphocytic leukemia criteria
Measured: 84 days after start of the last induction cycle
Secondary outcomes (2)
Adverse Events (AEs) and adverse events of special interest (AESI)
Type, frequency and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment
Measured: up to 40 months after first dose of study drug
Rate of minimal residual disease (MRD)
Rate of MRD responses in peripheral blood measured by immunophenotyping
Measured: up to 40 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2015 (estimated)
- Study start28 May 2015
- Primary completion9 Mar 2022
- Study completion9 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- German CLL Study Group
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche, Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Paula Cramer, Dr. med., Principal investigator, German CLL Study Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02445131
- Sponsor's protocol ID
- CLL2-BCG
- Other IDs
- 2014-000582-47, 2014
- Status last verified
- Jul 2023
- First submitted
- 5 May 2015
- Last updated
- 9 May 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, Fink AM, Furstenau M, Kutsch N, Simon F, Goede V, Hoechstetter M, Niemann CU, da Cunha-Bang C, Kater A, Dubois J, Gregor M, Staber PB, Tausch E, Schneider C, Stilgenbauer S, Eichhorst B, Fischer K, Hallek M. Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies. Blood. 2024 Jun 20;143(25):2588-2598. doi: 10.1182/blood.2023022564.
PubMed 38620092
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Open-label, Multicenter Phase-II Trial to Evaluate Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by GA101 (Obinutuzumab) and CAL-101 (Idelalisib) Followed by CAL-101 and GA101 Maintenance in CLL Patients
- ClinicalTrials.gov ID
- NCT02445131
- Acronym / sponsor ID
- CLL2-BCG
- Conditions
- Chronic Lymphocytic Leucemia
- Keywords
- CLL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- German CLL Study GroupUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche, Gilead Sciences
- Study start
- 28 May 2015 (actual)
- Primary completion
- 9 Mar 2022 (actual)
- Study completion
- 9 Mar 2022 (actual)
- First posted
- 15 May 2015 (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.
The CLL2-BCG-trial is a prospective, open-label, multicenter phase-II-trial to evaluate the efficacy and safety of a sequential regimen of a debulking with bendamustine followed by an induction with GA101 (obinutuzumab) and CAL-101 (idelalisib) followed by CAL-101 and GA101-maintenance in CLL patients
Detailed description
In the CLL2-BCG-trial, a total of 62 patients of an allcomer CLL population (irrespective of physical fitness, previous therapies and prognostic factors) with an indication for treatment will be included. Patients will receive 2 cycles of debulking treatment with bendamustine unless contraindications (e.g. refractoriness) are present or a debulking is not indicated due to a low tumor burden. Afterwards, 6 cycles of induction treatment with GA101 (obinutuzumab, 3 doses in the first cycle and monthly in cycles 2-6) and CAL-101 (idelalisib, continuously starting in cycle 2) will be applied. The primary endpoint overall response rate will be assessed at final restaging (2 months after end of induction treatment). Patients benefitting from treatment receive further therapy with GA101 (3 monthly) and CAL-101 (continuously) in a maintenance phase for up to 24 months. Maintenance treatment will be stopped in case of achievement of a complete remission and confirmation of MRD (minimal residual disease) negativity in peripheral blood or if unacceptable toxicity or progression occurs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bendamustine + GA101 + CAL-101 | Experimental | Drug: Bendamustine, Drug: GA101, Drug: CAL-101Bendamustine: 70 mg/m2 i.v. GA101: 1000 mg CAL-101: 150 mg p.o. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- documented chronic lymphocytic leukemia (CLL) requiring treatment according to International Working Group on CLL (iwCLL) criteria
- adequate hematologic function: platelets ≥ 25.000/µl, neutrophils ≥ 1.000/µl and hemoglobin ≥8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
- adequate renal function: a creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection
- adequate liver function: total bilirubin ≤1,5x, aspartate aminotransferase (AST) / alanin aminotransferase (ALT) ≤2.5x the institutional upper limit of normal (ULN) value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
- negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
Key exclusion criteria (16 listed)
- transformation of CLL (i.e. Richter's transformation, prolymphocytic leukemia)
- known central nervous system (CNS) involvement
- confirmed progressive multifocal leukoencephalopathy (PML)
- malignancies other than CLL currently requiring systemic therapies
- uncontrolled infection requiring systemic treatment
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 |
|---|---|---|
| BendamustineDebulking: Cycles 1 - 2, d1 \& 2: 70 mg/m2 i.v. | Drug | Bendamustine + GA101 + CAL-101 |
| GA101Also: ObinutuzumabInduction: Cycle 1: d1: 100mg, d1(or2): 900mg, d8 \& 15: 1000mg; Cycle 2-6: d1: 1000mg Maintenance: Cycle 1-8 (Duration 12 weeks): d1 1000 mg. | Drug | Bendamustine + GA101 + CAL-101 |
| CAL-101Also: IdelalisibInduction: Cycle 2-6: d1-28: 150 mg p.o. Maintenance: Cycles 1-8 (Duration 12 weeks): d1-84 150 mg p.o. | Drug | Bendamustine + GA101 + CAL-101 |
Primary outcome
Overall response rate (ORR)
Time frame: 84 days after start of the last induction cycle
Proportion of patients responding according to international working Group on chronic lymphocytic leukemia criteria
2 secondary outcomes
Adverse Events (AEs) and adverse events of special interest (AESI)
Time frame: up to 40 months after first dose of study drug
Rate of minimal residual disease (MRD)
Time frame: up to 40 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2024.
- Derived from this study: PubMed 38620092Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, Fink AM, Furstenau M, Kutsch N, Simon F, Goede V, Hoechstetter M, Niemann CU, da Cunha-Bang C, Kater A, Dubois J, Gregor M, Staber PB, Tausch E, Schneider C, Stilgenbauer S, Eichhorst B, Fischer K, Hallek M. Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies. Blood. 2024 Jun 20;143(25):2588-2598. doi: 10.1182/blood.2023022564.
- Publication on primary endpoint analysisLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Chronic Lymphocytic Leucemia
RecruitingObservational study
LEF1 EXPRESSION IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS: A MARKER FOR DIAGNOSIS AND SURVIVAL PREDICTION
Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
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.
Paula Cramer, Dr. med. principal investigator
German CLL Study Group
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 Bendamustine, GA101 and CAL-101 in people with Chronic Lymphocytic Leucemia, run by German CLL Study Group 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 9 inclusion and 16 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: finished, as of the sponsor's last update on 9 May 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall response rate (ORR) (time frame: 84 days after start of the last induction cycle). 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 NCT02445131, which also lists 1 linked publication.
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 9 May 2024.