Sequential Regimen of Bendamustine-Debulking Followed by CAL-101 and GA101-Induction and -Maintenance in CLL (CLL2-BCG)

NCT02445131 | Completed Phase 2

• 2 other identifiers: CLL2-BCG2014-000582-47
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Chronic Lymphocytic Leucemia

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Proportion of patients responding according to international working Group on chronic lymphocytic leukemia criteria

  84 days after start of the last induction cycle

Secondary Outcomes (2)

• Adverse Events (AEs) and adverse events of special interest (AESI)

  up to 40 months after first dose of study drug

• Rate of minimal residual disease (MRD)

  up to 40 months

Study Arms (1)

Bendamustine + GA101 + CAL-101

EXPERIMENTAL

Bendamustine: 70 mg/m2 i.v. GA101: 1000 mg CAL-101: 150 mg p.o.

Drug: Bendamustine; Drug: GA101; Drug: CAL-101

Interventions

Bendamustine DRUG

Debulking: Cycles 1 - 2, d1 \& 2: 70 mg/m2 i.v.

Bendamustine + GA101 + CAL-101

GA101 DRUG

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.

Also known as: Obinutuzumab

Bendamustine + GA101 + CAL-101

CAL-101 DRUG

Induction: Cycle 2-6: d1-28: 150 mg p.o. Maintenance: Cycles 1-8 (Duration 12 weeks): d1-84 150 mg p.o.

Also known as: Idelalisib

Bendamustine + GA101 + CAL-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• German CLL Study Group: lead
• Hoffmann-La Roche: collaborator
• Gilead Sciences: collaborator

Study Sites (1)

German CLL Study Group

Cologne, 50935, Germany

Location

Related Publications (1)

• 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.

  PMID: 38620092 DERIVED

Related Links

• Publication on primary endpoint analysis

MeSH Terms

Interventions

Bendamustine Hydrochloride; obinutuzumab; idelalisib

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Paula Cramer, Dr. med.

  German CLL Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 15, 2015
• Study Start: May 28, 2015
• Primary Completion: March 9, 2022
• Study Completion: March 9, 2022
• Last Updated: May 9, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)