Combination of PCI-32765 With Obinutuzumab in Untreated Follicular Lymphoma

NCT02689869 | Unknown Phase 2 DMC

• 1 other identifier: 2014-005164-15
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives The primary objective of this study is to evaluate the efficacy of the chemotherapy-free combination of ibrutinib and obinutuzumab (GA 101) in patients with previously untreated follicular lymphoma (FL) and a high tumor burden. Primary endpoint to be observed for this is the rate of progression free survival one year after start of therapy. Hypothesis The hypothesis of the study is that ibrutinib in combination with obinutuzumab will achieve response rates (CR and PR), rates of MRD negativity and PFS which are comparable to currently used standard rituximab-chemotherapy combinations such as R-CHOP or R-bendamustine in subjects with previously untreated FL and a high tumor burden.

Conditions

Indolent Non-Hodgkin Lymphoma

Keywords

indolent lymphoma; novel agents; chemotherapy free treatment; ibrutinib; obinutuzumab; GA101

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  The rate of patients archiving a progression free survival of more than one year after registration (one-year PFS) will serve as early readout for efficacy and will be the primary endpoint of this trial.

  one year progress free survival

Secondary Outcomes (14)

• three-year-PFS

  three years after start of therapy

• CR

  one year after start of therapy and at 30 months after end of maintenance

• PR

  one year after start of therapy and at 30 months after end of maintenance

• SD

  one year after start of therapy and at 30 months after end of maintenance

• Duration of response

  4,5 up to 6,5 years through study completion

Study Arms (1)

Ibrutinib and GA 101

EXPERIMENTAL

Initial therapy 6 cycles of Ibrutinib: Ibrutinib 560 mg once daily every day until start of maintenance for a total of 24 weeks. 1000 mg of GA101 I.V. on days d 1, 8, 15 of cycle 1 and on day 1 of cycles 2-6 (21 day cycles). Maintenance with another 24 months of ibrutinib plus GA101 in patients with clinical remission after the last induction cycle: Ibrutinib 560 mg once daily every day. GA101 at a dose of 1000 mg I.V. every 2 months for a total of 24 months. The total duration of ibrutinib plus obinutuzumab therapy will therefore be 30 months. In patients remaining MRD positive at 30 months without clinical progression, single agent ibrutinib therapy is continued for another 12 months.

Drug: Ibrutinib; Drug: GA 101

Interventions

Ibrutinib DRUG

Ibrutinib (PCI-32765; JNJ-54179060) is a first-in-class, potent, orally-administered covalently-binding small molecule inhibitor of Bruton's tyrosine kinase currently being co-developed by Janssen Research \& Development, LLC and Pharmacyclics, Inc for the treatment of B-cell malignancies.

Also known as: Imbruvica

Ibrutinib and GA 101

GA 101 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: Obinutuzumab

Ibrutinib and GA 101

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed follicular lymphoma grade 1, 2 or 3A with a lymph node biopsy performed within 12 months before study entry and with material available for central review and complementary scientific analyses
• Ann Arbor stage III/IV, or stage II not suitable for radiotherapy, or stage II bulky disease
• Age ≥ 18 years
• No prior lymphoma therapy
• Need for start of therapy as defined by:
• bulky disease at study entry according to the GELF criteria (nodal or extranodal mass \>7 cm in its greater diameter)
• and/or B symptoms (fever, drenching night sweats, or unintentional weight loss of \>10% of normal body weight over a period of 6 months or less)
• and/or hematopoietic insufficiency (granulocytopenia \< 1.500/µl, Hb \< 10 g/dl, thrombocytopenia \< 100.000/µl)
• compressive syndrome or high risk for compression syndrome
• and/or pleural/peritoneal effusion
• and/or symptomatic extranodal manifestations
• At least one bi-dimensionally measurable lesion (\> 2 cm in its largest dimension by CT scan or MRI)
• Performance status ≤ 2 on the ECOG scale
• Adequate hematologic function (unless abnormalities are related to NHL), defined as follows:
• Hemoglobin ≥ 9.0 g/dL

You may not qualify if:

• \- Transformation to high-grade lymphoma (secondary to "low grade" FL)
• Grade 3B follicular lymphoma
• Presence or history of CNS disease (either CNS lymphoma or leptomeningeal lymphoma).
• Known hypersensitivity to any of the study drugs
• Known sensitivity to murine products
• Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to \< 20 mg/day prednisone.
• Concomitant use of strong CYP3A4 inhibitors and / or oral anticoagulants (warfarin and/or phenprocoumon)
• Prior or concomitant malignancies except:
• non-melanoma skin cancer or adequately treated in carcinoma in situ of the cervix
• Other malignant diseases not specified above which have been curatively treated by surgery alone and from which subject is disease-free for ≥5 years without further treatment
• Serious disease interfering with a regular therapy according to the study protocol:
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• pulmonary (e.g. chronic lung disease with hypoxemia)
• endocrine (e.g. severe, not sufficiently controlled diabetes mellitus)
• renal insufficiency (unless caused by the lymphoma): creatinine \> 2x normal value and/or creatinine clearance \< 50 ml/min)

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead
• Hoffmann-La Roche: collaborator
• Janssen-Cilag G.m.b.H: collaborator

Study Sites (1)

Klinikum der Universität München

München, Bavaria, 81377, Germany

Location

MeSH Terms

Interventions

ibrutinib; obinutuzumab

Study Officials

• Wolfgang Hiddemann, Prof.

  Klinikum der Universität München

  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: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. W. Hiddemann

Study Record Dates

• First Submitted: February 4, 2016
• First Posted: February 24, 2016
• Study Start: April 1, 2016
• Primary Completion: April 1, 2022
• Study Completion: July 1, 2022
• Last Updated: May 7, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)