Direkt zum Inhalt | Direkt zur Navigation

Benutzerspezifische Werkzeuge

Sektionen
Studienregister
Sie sind hier: Startseite / Klinische Studien / Studienregister

Studienregister

CLL2-BAAG

AcronymISRCTNEudraCTClinicaltrials.govDRKS
2017-003133-28

A prospective, open-label, multicenter phase-II-trial to evaluate the efficacy and safety of a sequential regimen of Bendamustin followed by GA101 (Obinutuzumab), Acalabrutinib (ACP-196) and ABT-199 (Venetoclax) in patients with relapsed/refractory CLL (CLL2-BAAG-trial of the GCLLSG)

Status: Active

Purpose / Objectives

Primary Outcome

    • Negativity rate of minimal residual disease (MRD) in peripheral blood (PB) measured by 4-color flow at final restaging after end of induction treatment

Secondary Outcomes

  • Overall response rate (ORR) at final restaging (RE) 12 weeks after the start of the last cycle of induction therapy (end of induction treatment response = EOIT) including all patients achieving:
    • a (clinical) complete response ((clinical) CR),
    • a (clinical) CR with incomplete recovery of the bone marrow ((clinical) CRi)
    • a partial response (PR), or
  • a partial response with lymphocytosis (PR-L).
  • Safety parameters: Type, frequency, and severity of adverse events (AE) and, adverse events of special interest (AESI) and their relationship to study treatment

  • MRD in PB measured by by 4-color flow to guide the duration of maintenance therapy at:

    • final restaging after end of induction treatment (12 weeks after last cycle of induction treatment) in all patients responding to study treatment and

    • every 12 weeks (= 3 months) during the maintenance phase if the patient has achieved a (clinical) CR/CRi (or PR almost fulfilling CR criteria, e.g. with residual splenomegaly) or

    • every 24 weeks (= 6 months) in patients with a PR/ PR-L.

and MRD in PB measured by by 4-color flow for the assessment of the kinetics of response to the different treatment phases at:

  • screening/baseline
  • staging after debulking (if applicable)
  • before start with ACP-196 (cycle 2, d1)
  • before start with ABT-199 (cycle 3, d1)
  • interim staging (after 3 induction cycles)
  • initial response assessment (after 6 induction cycles)
  • MRD in bone marrow measured by 4-color flow optionally in patients with (clinical) CR/CRi (or PR almost fulfilling CR criteria, e.g. with residual splenomegaly) 3 months after achievement of MRD negativity in peripheral blood

  • [...]

 

Diagnosis

Patient attributes

Age

18-99

Inclusion criteria

  • Relapsed/refractory CLL in need of treatment according to iwCLL criteria(1) 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 within ≥ 28 days
  • antibody treatment within ≥ 14 days
  • kinase inhibitors, BCL2-antagonists or immunmodulatory agents within ≥ 3 days
  • corticosteroids may be applied until the start of the BAAG-regimen, these have to be reduced to an equivalent of ≤ 20mg prednisolon during treatment

Please note: Patients with a progression or intolerance to ibrutinib are eligible for participation

  • 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 platelet count ≥ 25 x 109/L, a neutrophil count ≥ 1,0 x 109/L and a hemoglobin value ≥8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
  • 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 negative 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 month until 1 year after last dosage of GA101 (obinutuzumab)), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
  • ECOG 0-2
  • [...]

Exclusion criteria

  • (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, ib-rutinib 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, exclud-ing 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 gastroin-testinal tract)
  • Significantly increased risk of bleeding according to the investigator´s evaluation, e.g. due known bleeding diathe-sis (e.g. von-Willebrandt´s disease or hemophilia), major surgical procedure ≤ 4 weeks or stroke/intracranial hem-orrhage ≤ 6 months.
  • [...] 

Trial design

  • Phase II
  • Multicenter
  • Prospective
  • One-arm
  • Open Label

Documents (password protected)

Responsibilities in overall trial

Universität zu Köln

  • Tel. +49 (0)221 478 0

National Coordinating Investigator

Dr. med. Paula Cramer

Study Sites

Klinik I für Innere Medizin

Study office

  • Klinisches Studienzentrum der Klinik I für Innere Medizin Köln

Status

Active

Principal Investigator

Dr. med. Paula Cramer

Deputy of Principal Investigator

  • Prof. Dr. med. Barbara Eichhorst
  • Univ.-Prof. Dr. med. Michael Hallek

Subinvestigator

  • Dr. med. Janine Böll, geb. Schwamb
  • Dr. med. Moritz Fürstenau
  • Dr. med. Anja Jühling
  • Florian Simon
  • Dr. med. Armin Tuchscherer
  • PD Dr. med. Stephanie Sasse
  • Dr. med. Birgit Cremer
  • Prof. Dr. med. Christian Pallasch
  • Priv.-Doz. Dr. med. Bastian von Tresckow
  • PD Dr. med. Thomas Zander
  • Dr. med. Julia von Tresckow, geb. Kilp
  • Dr. med. Othman Al-Sawaf
  • Univ.-Prof. Dr. med. Dr. rer.-nat. Roland Ullrich
  • Johanna Prinz
  • Dr. med. Nadine Kutsch
  • Dr. Stefanie Kreissl
  • Dr. med. Carmen Diana Herling
  • Carolin Groß-Ophoff-Müller
  • Dr. med. Ron Jachimowicz
  • Dr. med. Paul Bröckelmann
  • Dr. med. Petra Langerbeins, geb. Jenke

Contact at Site