First Line Therapy of Advanced Stage Follicular Lymphoma in Patients < 60 Years Not Eligible fo Standard Immunochemotherapy and in All Patients ≥ 60 Years

NCT03492775 | Completed Phase 2 DMC

• 1 other identifier: 2016-000755-27
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to test the efficacy and toxicity of a combined OBINUTUZUMAB/bendamustine therapy or single agent OBINUTUZUMAB in younger (\< 60 years) medically non-fit, 'compromised' patients and in all older patients (≥ 60 years). For the assessment of the antilymphoma activity the overall response rate (ORR)" will be applied as primary endpoint. Overall response is defined as complete or partial response after 19 - 21 weeks.

Conditions

Indolent Non-hodgkin Lymphoma

Keywords

indolent lymphoma; Obinutuzumab; GA101; Bendamustine; medically non-fit patients

Outcome Measures

Primary Outcomes (1)

• ORR

  Overall response is defined as complete or partial response at the end of the initial treatment phase (after 19-21 weeks).

  week 19 to 21

Secondary Outcomes (18)

• Event free survival, EFS

  through study completion, up to 5 years

• CR

  End of Induction of each patient, week 19 - 21

• TTF

  Through study completion, up to 5 years

• PFS

  Through study completion, up to 5 years

• RD

  week 19 up to 5,5 years follow up

Study Arms (2)

Arm A:Obinutuzumab single agent

ACTIVE COMPARATOR

Obinutuzumab flat dose of 1000 mg on Day 1 of each of four 28 -day cycles and on Days 8 and 15 of Cycle 1 If at least 'stable disease': Obinutuzumab flat dose of 1000 mg at weeks 21, 29, 37 and 45

Drug: Obinutuzumab

Arm B:Obinutuzumab plus Bendamustine

ACTIVE COMPARATOR

Obinutuzumab flat dose of 1000 mg on Day 1 of each of four 28 -day cycles and on Days 8 and 15 of Cycle 1 plus Bendamustine 70 mg/m2 iv d1+2 of each of four 28 -day cycles If at least 'stable disease': Obinutuzumab flat dose of 1000 mg at weeks 21, 29, 37 and 45

Drug: Obinutuzumab; Drug: Bendamustine

Interventions

Obinutuzumab DRUG

Obinutuzumab (GA 101) is a first-in-class, potent, intravenously administered type II anti-CD 20 antibody that is developed by Roche AG for the treatment of B-cell malignancies.

Also known as: GA 101

Arm A:Obinutuzumab single agent; Arm B:Obinutuzumab plus Bendamustine

Bendamustine DRUG

Bendamustine belongs formally to the alkylators, but has been shown to have a unique mechanism of action. The dose limiting toxicity of bendamustine is its reversible suppression of bone marrow function with drops in leukocyte and thromobocyte counts.

Also known as: Bendamustine hydrochloride; Ribomustin

Arm B:Obinutuzumab plus Bendamustine

Eligibility Criteria

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

You may qualify if:

• Medically nonfit" patients \< 60 years defined by
• o ECOG \> 2 or ECOG 0-2 with co-morbidities excluding intensive therapy according to local investigator's discretion
• All patients ≥ 60 years in case of decision of investigator and patient to apply a reduced Treatment
• Documentation of the CIRS-G, IADL, G8 and ECOG Scores before start of treatment
• Histologically confirmed follicular lymphoma grade I, II or IIIa with material available for central pathology review
• Stage III/IV or stage II without the option of curative radiotherapy
• Age \> 18 years
• No prior therapy
• Presence of at least one of the following symptoms or conditions requiring initiation of treatment:
• Bulky disease according to the GELF criteria: nodal or extranodal mass \> 7cm in its greater diameter
• B symptoms (fever, drenching night sweats, or unintentional weight loss of \>10% of normal body weight over a period of 6 months or less)
• Hematopoietic insufficiency (at least one of the following: granulocytopenia \<1500 cells/μl, Hb \< 10 g/dl, thrombocytopenia \<100.000 cells/μl)
• Compressive syndrome
• Pleural/peritoneal effusion
• Symptomatic nodal or extranodal manifestations

You may not qualify if:

• "Medically fit" patients \< 60 years with the option for more intensive induction therapy such as R-CHOP
• Transformation to high-grade lymphoma (secondary to "low-grade" follicular lymphoma)
• Grade IIIb follicular lymphoma
• Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis).
• Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to \< 20 mg/day prednisone.
• Prior (\< 3 years) or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer.
• Major surgery (excluding lymph node biopsy) within 28 days prior to registration.
• Necessity of rapid cytoreduction
• Serious underlying medical conditions, which could impair the ability of the patient to tolerate the therapy offered in this trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease).
• Severe hepatic impairment (serum bilirubin \> 3.0 mg/dl)
• Known sensitivity or allergy to murine products
• Known hypersensitivity to any of the study drugs
• Treatment within a clinical lymphoma trial within 30 days prior to trial entry
• Positive test results for chronic HBV infection (defined as positive HBsAg serology) (mandatory testing) Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody (HBSAb) after vaccination or prior but cured hepatitis B are eligible.
• Positive test results for hepatitis C (mandatory hepatitis C virus \[HCV\] antibody serology testing). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA

Sponsors & Collaborators

• Prof. Dr. Wolfgang Hiddemann: lead
• Hoffmann-La Roche: collaborator
• Mundipharma Research GmbH & Co KG: collaborator

Study Sites (1)

Klinikum der Universität München

München, Bavaria, 81377, 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

• Wolfgang Hiddemann, Prof.Dr.

  Hospital of the University of Munich

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. Wolfgang Hiddemann

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: April 10, 2018
• Study Start: December 12, 2017
• Primary Completion: November 30, 2021
• Study Completion: December 31, 2022
• Last Updated: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)