CLLR3: Bendamustine + GA101 (BG) in Relapsed or Refractory CLL Followed by GA101 Maintenance for Responding Patients

NCT02320383 | Unknown Phase 2

• 1 other identifier: CLLR3
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Chronic Lymphocytic Leucemia

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• 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).

  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 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)

  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)

  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)

  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

  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

Study Arms (1)

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

Biological: GA101 (Obinutuzumab); Drug: Bendamustine

Interventions

GA101 (Obinutuzumab) BIOLOGICAL

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

Also known as: Gazyvaro

B + GA101

Bendamustine DRUG

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

Also known as: Ribomustin, Levact

B + GA101

Eligibility Criteria

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

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Munich Municipal Hospital: lead
• German CLL Study Group: collaborator

Study Sites (1)

German CLL Study Group

Cologne, 50923, Germany

Location

MeSH Terms

Interventions

obinutuzumab; Bendamustine Hydrochloride

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

• Clemens-Martin Wendtner, Prof. Dr.

  Klinikum München GmbH

  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: September 1, 2014
• First Posted: December 19, 2014
• Study Start: November 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: September 1, 2022
• Last Updated: August 13, 2018

Record last verified: 2018-08

Locations

DE (1)