AzTrials
AzTrials

Chronic Lymphoid LeukemiaPhase 2CLL2-BAAGNCT03787264

Sequential Regimen of Bendamustin-Debulking Followed by Obinutuzumab, Acalabrutinib and Venetoclax in Patients With Relapsed/Refractory CLL

A Phase 2 study testing Bendamustine, Obinutuzumab and Acalabrutinib in people with Chronic Lymphoid Leukemia, run by German CLL Study Group at 17 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

CLL2-BAAG is a prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of debulking with bendamustine followed by induction and maintenance with GA101 (obinutuzumab), acalabrutinib (ACP-196) and venetoclax (ABT-199) in patients with relapsed/refractory CLL. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphoid Leukemia
What is being tested?
Bendamustine, Obinutuzumab and Acalabrutinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
17 sitesGermany
Study dates
14 Jan 2019to 26 Sep 2023
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

  • Relapsed/refractory CLL in need of treatment according to iwCLL (international workshop on CLL) criteria
  • In case of a recent previous treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods before start of the study treatment in the CLL2-BAAG trial:
  • chemotherapy ≥ 28 days
  • antibody treatment ≥ 14 days
  • kinase inhibitors, BCL2-antagonists or immuno-modulatory agents ≥ 3 days
  • corticosteroids may be applied until the start of the BAAG-regimen, these have to be reduced to an equivalent of ≤ 20mg prednisolone per day during treatment Please note: Patients with a progression during previous treatment with venetoclax, ibrutinib or another BTK inhibitor, as well as patients with a known resistance mutation (e.g. BTK-/PLCg2) are excluded from study participation. However, patients who progressed after termination of treatment with venetoclax, ibrutinib, other BTK inhibitors and/or obinutuzumab or who stopped treatment due to in-tolerance to ibrutinib are eligible for participation.
Show all 14Show fewer
  • Adequate renal function, as indicated by a creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection
  • Adequate hematologic function as indicated by a neutrophil count ≥ 1.0 x 109/L, a hemoglobin value ≥8.0 g/dL and a platelet count ≥ 25 x 109/L, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration), in this case, platelet count should be ≥ 10 × 109/L.
  • Adequate liver function as indicated by a total bilirubin ≤2x, AST/ALT ≤2.5x the institutional ULN value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
  • Negative serological testing for hepatitis B (HBsAg nega-tive and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every 4 weeks until one year after last dosage of GA101 (obinutuzumab)), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
  • Age ≥ 18 years
  • ECOG (Eastern Cooperative Oncology Group) performance status 0 - 2, ECOG 3 is only permitted if related to CLL (e.g. due to anemia or severe constitutional symptoms)
  • Life expectancy ≥ 6 months
  • Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other proto-col requirements

Who cannot join

  • (Suspicion of) transformation of CLL (i.e. Richter's trans-formation, pro-lymphocytic leukemia) or central nervous system (CNS) involvement
  • Progression during previous treatment with venetoclax, ibrutinib or another BTK inhibitor, and/or presence of known mutations associated with resistance to therapy, e.g. Bru-ton´s Tyrosine Kinase and Phospholipase C Gamma 2 (PLCg2)
  • 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 CIRS (cumulative illness rating scale) score of 4, excluding the eyes/ears/nose/throat/larynx organ system1 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)
Show all 18Show fewer
  • Significantly increased risk of bleeding according to the investigator´s evaluation, e.g. due known bleeding diathesis (e.g. von-Willebrandt´s disease or hemophilia), major surgical procedure ≤ 4 weeks or stroke/intracranial hemorrhage ≤ 6 months.
  • Requirement of therapy with strong CYP3A4 inhibitors/inducers or anticoagulant with phenprocoumon (marcumar) or other vitamin K-antagonists
  • Use of investigational agents ≤ 28 days prior to start of study treatment, however, kinase inhibitors, BCL2-antagonists and antibody treatment are allowed in accordance with inclusion criterion number 1 (see above).
  • Known hypersensitivity to obinutuzumab (GA101), venetoclax (ABT-199), acalabrutinib (ACP-196) or any of the excipients Please note: Patients with a known hypersensitivity to bendamustine are allowed to participate but will not receive a debulking with bendamustine
  • Pregnant women and nursing mothers (a negative preg-nancy test is required for all women of childbearing potential within 7 days before start of treatment)
  • 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 regula-tory or court order
  • Persons who are in dependence to the sponsor or an investigator

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

Germany17 sites

  • Universitätsklinik Köln

    Cologne, 50937

  • Gemeinschaftspraxis Hämatologie Onkologie

    Dresden, 1307

  • Gemeinschaftspraxis Mohm/Prange-Krex

    Dresden, 1307

  • Universitatsklinik Carl Gustav Carus

    Dresden, 1307

  • Helios Klinikum Erfurt

    Erfurt, 99089

  • Universitaetsklinikum Heidelberg

    Heidelberg, 69120

  • Universitaetsklinikum Jena

    Jena, 7747

  • Praxis fuer Haematologie und Onkologie

    Koblenz, 56068

  • Gemeinschaftspraxis Haemato/ Onkologie Lebach

    Lebach, 66822

  • Klinikum Leverkusen GmbH

    Leverkusen, 51375

  • Ludwig-Maximilians-Universitaet Muenchen

    München, 81377

  • Krankenhaus Muenchen-Schwabing

    Munich, 80804

  • Praxis Dr. Uhlig

    Naunhof, 4683

  • Universitätsklinik Rostock

    Rostock, 18057

  • ZAHO-Rheinland

    Siegburg, 53721

  • Universitaetsklinik Tuebingen

    Tübingen, 72076

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official title: A Prospective, Open-label, Multicenter Phase-II Trial to Evaluate the Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by GA101 (Obinutuzumab), Acalabrutinib (ACP-196) and ABT-199 (Venetoclax) in Patients With Relapsed/Refractory CLL (CLL2-BAAG Protocol)

CLL2-BAAG is a prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of debulking with bendamustine followed by induction and maintenance with GA101 (obinutuzumab), acalabrutinib (ACP-196) and venetoclax (ABT-199) in patients with relapsed/refractory CLL.

Read the detailed description

In the CLL2-BAAG trial will be included a total of 46 patients with relapsed or refractory CLL in need of treatment.This trial will evaluate a debulking with two cycles bendamustine (only for patients with a higher tumor load), followed by an induction and a maintenance treatment with obinutuzumab, acalabrutinib and venetoclax in patients with re-lapsed/refractory CLL. The duration of maintenance treatment is depending on MRD levels. This trial combines one old (chemotherapy) and three novel, synergistic (antibody, BTK-inhibitor and Bcl-2 antagonist) principles of action in order to achieve deep and long lasting remissions with a short duration of treatment. Additionally, this trial has an extensive accompanying scientific program aiming at a better understanding of the kinetics of response and clonal evolution of CLL.

Being tested
Bendamustine, Obinutuzumab, Acalabrutinib, Venetoclax
Medical subject headings
Leukemia, B-Cell

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 - 70mg/m² i.v.

  • ObinutuzumabBiological

    Also called GA101, Gazyvaro

    Induction: Cycle 1: d1 - 100 mg, d1 (or d2) - 900 mg, d8 + d15 - 1000 mg i.v.; Cycle 2 - 6: 1000 mg, d1 i.v.

    Maintenance: Cycle 1 - 8: 1000 mg, d1 i.v.

  • AcalabrutinibBiological

    Also called ACP-196, Calquence

    Induction: Cycle 1: --; Cycles 2 - 6: d1-28: 2 x 100mg p.o.

    Maintenance: Cycle 1 - 8: d1-84: 2 x 100mg p.o.

  • VenetoclaxBiological

    Also called ABT-199, Venclyxto

    Induction: Cycles 1 + 2: --; Cycle 3: d1-7: 20mg, d8-14: 50mg, d15-21: 100mg, d22-28: 200mg p.o.; Cycle 4 - 6: d1-28: 400 mg p.o.

    Maintenance: Cycle 1 - 8: d1-84: 400 mg p.o.

Study groups in NCT03787264
Study groupRoleWhat they receive
BAAGExperimentalDebulking: 2 debulking cycles (q 28d) of bendamustine will be administered unless the patient has a contraindication or a debulking is not clinically indicated Induction: 6 cycles (q 28d) of Obinutuzumab + Acalabrutinib + Venetoclax Maintenance: max. 8 cycles (q 84d) of Obinutuzumab + Acalabrutinib + Venetoclax Maintenance treatment will be continued until (whichever occurs first): * 12 weeks (approx. 3 months) after confirmation of achievement of a CR/CRi and MRD negativity * maintenance cycle 8 * progression of CLL or start of a subsequent therapy * unacceptable toxicity
Receives: Drug: Bendamustine; Biological: Obinutuzumab; Biological: Acalabrutinib; Biological: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Negativity rate of minimal residual disease (MRD) in peripheral blood (PB) measured by 4-color flow cytometry

    MRD negativity is defined as less than one (1) CLL-cell among 10,000 leukocytes analyzed [0.01%], i.e. < 10-4. The MRD negativity rate is defined as the proportion of patients having achieved MRD negativity based on the full analysis set (FAS).

    Measured: At final restaging (RE): 12 weeks after the start of the last induction cycle

Secondary outcomes (4)

  1. Overall response rate (ORR)

    Proportion of patients having achieved a complete response (CR), a CR with incomplete recovery of the bone marrow (CRi), or a partial response(PR) as best response.

    Measured: At final restaging (RE): 12 weeks after the start of the last induction cycle

  2. CR / CRi rate

    Proportion of patients having achieved a CR or CRi as best response

    Measured: At final restaging (RE): 12 weeks after the start of the last induction cycle

  3. MRD in PB measured by 4-color flow cytometry at different times: At screening, after debulking, 4-weekly during induction, at initial response assessment (after 6 induction cycles), at RE, every 12 weeks during maintenance and follow up.

    MRD negativity is defined as less than one (1) CLL-cell among 10,000 leukocytes analyzed [0.01%], i.e. < 10-4. MRD values will be categorized into negative (<10-4) and positive (≥10-4)

    Measured: From date of screening until the end of follow-up, up to 40 month.

  4. Safety: Adverse events (AE), serious adverse events (SAE) and adverse events of particular interest (AEPI)

    Type, frequency, and severity of AEs, SAEs and AESIs and their relationship to study treatment.

    Measured: up to 40 months after first dose of study drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Dec 2018
  2. Study start14 Jan 2019
  3. Primary completion11 Feb 2021
  4. Study completion26 Sep 2023

Resources

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
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03787264
Sponsor's protocol ID
CLL2-BAAG
Acronym
CLL2-BAAG
Status last verified
Nov 2023
First submitted
20 Dec 2018
Last updated
30 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Furstenau M, Weiss J, Giza A, Franzen F, Robrecht S, Fink AM, Fischer K, Schneider C, Tausch E, Stilgenbauer S, Ritgen M, Schilhabel A, Bruggemann M, Eichhorst B, Hallek M, Cramer P. Circulating Tumor DNA-Based MRD Assessment in Patients with CLL Treated with Obinutuzumab, Acalabrutinib, and Venetoclax. Clin Cancer Res. 2022 Oct 3;28(19):4203-4211. doi: 10.1158/1078-0432.CCR-22-0433.

    PubMed 35594173

  • Cramer P, Furstenau M, Robrecht S, Giza A, Zhang C, Fink AM, Fischer K, Langerbeins P, Al-Sawaf O, Tausch E, Schneider C, Schetelig J, Dreger P, Bottcher S, Kreuzer KA, Schilhabel A, Ritgen M, Bruggemann M, Kneba M, Stilgenbauer S, Eichhorst B, Hallek M. Obinutuzumab, acalabrutinib, and venetoclax, after an optional debulking with bendamustine in relapsed or refractory chronic lymphocytic leukaemia (CLL2-BAAG): a multicentre, open-label, phase 2 trial. Lancet Haematol. 2022 Oct;9(10):e745-e755. doi: 10.1016/S2352-3026(22)00211-3. Epub 2022 Aug 18.

    PubMed 35988545

  • Furstenau M, Giza A, Weiss J, Kleinert F, Robrecht S, Franzen F, Stumpf J, Langerbeins P, Al-Sawaf O, Simon F, Fink AM, Schneider C, Tausch E, Schetelig J, Dreger P, Bottcher S, Fischer K, Kreuzer KA, Ritgen M, Schilhabel A, Bruggemann M, Stilgenbauer S, Eichhorst B, Hallek M, Cramer P. Acalabrutinib, venetoclax, and obinutuzumab in relapsed/refractory CLL: final efficacy and ctDNA analysis of the CLL2-BAAG trial. Blood. 2024 Jul 18;144(3):272-282. doi: 10.1182/blood.2023022730.

    PubMed 38620072

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bendamustine, Obinutuzumab and Acalabrutinib in people with Chronic Lymphoid Leukemia, run by German CLL Study Group at 17 sites 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 14 inclusion and 18 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 30 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites 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?

Negativity rate of minimal residual disease (MRD) in peripheral blood (PB) measured by 4-color flow cytometry (time frame: At final restaging (RE): 12 weeks after the 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 NCT03787264, which also lists 3 linked publications.

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 30 Dec 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in