Indolent Non-Hodgkin LymphomaPhase 2AlternativeNCT02689869
Combination of PCI-32765 With Obinutuzumab in Untreated Follicular Lymphoma
A Phase 2 study testing Ibrutinib and GA 101 in people with Indolent Non-Hodgkin Lymphoma, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Indolent Non-Hodgkin Lymphoma
- What is being tested?
- Ibrutinib and GA 101
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2016to Jul 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- Absolute neutrophil count ≥ 1500 /µl
- Platelet count ≥ 75000 /µl
- Women are not breast feeding, are using highly effective contraception, are not pregnant, and agree not to become pregnant during participation in the trial and during the 18 months thereafter (pregnancy testing is mandatory for premenopausal women).
- Men agree not to father a child during participation in the trial and during the 18 months thereafter.
- Written informed consent
Who cannot join
- - 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.
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- 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)
- impairment of liver function (unless caused by the lymphoma): transaminases > 3x normal or bilirubin > 2,0 mg/dl (unless caused by known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome])
- Positive test results for chronic HBV infection (defined as positive HBsAg serology) 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 (hepatitis C virus [HCV] antibody serology testing). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
- Known history of HIV seropositive status.
- Patients with a history of confirmed PML
- Vaccination with a live vaccine within 28 days prior to registration
- Recent major surgery (within 4 weeks prior to the start of Cycle 1)
- History of stroke or intracranial hemorrhage within 6 months prior to registration
- Serious underlying medical conditions, which could impair the ability of the patient to undergo the treatment offered in the study (e.g. ongoing infection, gastric ulcers, active autoimmune disease)
- Treatment within a clinical trial within 30 days prior to trial entry.
- Prior organ, bone marrow or peripheral blood stem cell transplantation
- Known or persistent abuse of medication, drugs or alcohol
- Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Chemotherapy-free Combination of the Bruton's Tyrosine Kinase Inhibitor, Ibrutinib in Combination With GA 101 in Patients With Previously Untreated Follicular Lymphoma and a High Tumor Burden
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.
Read the detailed description
OVERVIEW OF STUDY DESIGN This is a prospective, multicenter phase 2 study in up to 98 subjects with previously untreated FL and a high tumor burden in advanced stages and in need of therapy. The study will include a central monitoring of MRD by PCR, a central pathologic review and complimentary research projects including monitoring of immune response.
The study therapy comprises an initial 6 cycles of ibrutinib plus obinutuzumab followed by an additional 24 months of ibrutinib plus obinutuzumab maintenance.
In patients being MRD negative at 30 months, i.e. at the end of ibrutinib plus obinutuzumab maintenance, and without clinical progression no further treatment is given while MRD monitoring is continued.
MRD monitoring will be regularly performed on peripheral blood samples collected before the start of therapy and at months 3, 6, 9, 12, 18, 24 and 30 respectively. Subsequently, MRD analyses will be performed every 6 months until clinical progression of the disease or for a maximum of 4 years (until the end of the study).
If MRD assessment on peripheral blood samples turns from positive to negative within the first 30 months, confirmatory blood and bone marrow samples should be taken 6 months thereafter.
In patients remaining MRD positive at 30 months without clinical progression, single agent ibrutinib therapy is continued for another 12 months.
An independent Data Monitoring Committee (DMC) will be formed and constituted. The independent DMC will review the safety of the treatment and make recommendations as to the further conduct of the study.
The data generated by this phase II study should serve as the basis for a subsequent randomized phase III study comparing the chemotherapy-free combination of ibrutinib plus obinutuzumab with standard immune-chemotherapy.
- Conditions
- Indolent Non-Hodgkin Lymphoma
- Being tested
- Ibrutinib, GA 101
- Keywords
- indolent lymphoma, novel agents, chemotherapy free treatment, ibrutinib, obinutuzumab, GA101
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica
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.
GA 101Drug
Also called Obinutuzumab
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ibrutinib; Drug: GA 101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: one year progress free survival
Secondary outcomes (14)
three-year-PFS
Progression free survival after start of therapy (continuous observation)
- three-year-PFS
Measured: three years after start of therapy
CR
CR rates at end of induction CR rates one year after start of therapy CR rates after end of maintenance therapy (at 30 months after start of therapy: CR30)
Measured: one year after start of therapy and at 30 months after end of maintenance
PR
PR rates at end of induction PR rates one year after start of therapy PR rates after end of maintenance therapy (at 30 months after start of therapy: CR30)
Measured: one year after start of therapy and at 30 months after end of maintenance
SD
SD rates at end of induction
Measured: one year after start of therapy and at 30 months after end of maintenance
Duration of response
Duration of Response
Measured: 4,5 up to 6,5 years through study completion
Percentage of Progression
Percentage of progression during induction and maintenance therapy
Measured: 4,5 up to 6,5 years through study completion
TTF after start of therapy
Time to treatment failure after start of therapy (failure defined by failure to achieve a CR/PR after 6 months or progression after CR or PR or death in remission)
Measured: 4,5 up to 6,5 years through study completion
Time to next anti-lymphoma therapy / time to next chemotherapy based treatment
Time to next anti-lymphoma therapy and time to next chemotherapy based treatment
Measured: 4,5 up to 6,5 years through study completion
Treatment associated adverse events
Treatment associated adverse events
Measured: 4,5 up to 6,5 years through study completion
Percentage of MRD negative patients during therapy
Percentage of MRD negative patients during induction therapy (midterm), after induction therapy and after maintenance therapy
Measured: 4,5 up to 6,5 years through study completion
Duration of molecular remission
Duration of molecular remission for MRD negative patients after the end of induction and maintenance
Measured: 4,5 up to 6,5 years through study completion
Percentage of secondary transformation
Percentage of secondary Transformation to aggressive lymphoma
Measured: 4,5 up to 6,5 years through study completion
Percentage of secondary malignancies
Percentage of secondary malignancies
Measured: 4,5 up to 6,5 years through study completion
Time to first secondary malignancy
Time to first secondary malignancy
Measured: 4,5 up to 6,5 years through study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study startApr 2016
- Primary completionApr 2022 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Indolent Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche, Janssen-Cilag G.m.b.H
- Responsible party
- Principal investigator, Prof. Dr. Wolfgang Hiddemann, Ludwig-Maximilians - University of Munich
- Investigators
- Wolfgang Hiddemann, Prof., Principal investigator, LMU Klinikum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02689869
- Sponsor's protocol ID
- 2014-005164-15
- Other IDs
- 2014
- Acronym
- Alternative
- Status last verified
- May 2021
- First submitted
- 4 Feb 2016
- Last updated
- 7 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Chemotherapy-free Combination of the Bruton's Tyrosine Kinase Inhibitor, Ibrutinib in Combination With GA 101 in Patients With Previously Untreated Follicular Lymphoma and a High Tumor Burden
- ClinicalTrials.gov ID
- NCT02689869
- Acronym / sponsor ID
- Alternative / 2014-005164-15
- Conditions
- Indolent Non-Hodgkin Lymphoma
- Keywords
- indolent lymphoma, novel agents, chemotherapy free treatment, ibrutinib, obinutuzumab, GA101
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche, Janssen-Cilag G.m.b.H
- Study start
- Apr 2016
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 24 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OVERVIEW OF STUDY DESIGN This is a prospective, multicenter phase 2 study in up to 98 subjects with previously untreated FL and a high tumor burden in advanced stages and in need of therapy. The study will include a central monitoring of MRD by PCR, a central pathologic review and complimentary research projects including monitoring of immune response.
The study therapy comprises an initial 6 cycles of ibrutinib plus obinutuzumab followed by an additional 24 months of ibrutinib plus obinutuzumab maintenance.
In patients being MRD negative at 30 months, i.e. at the end of ibrutinib plus obinutuzumab maintenance, and without clinical progression no further treatment is given while MRD monitoring is continued.
MRD monitoring will be regularly performed on peripheral blood samples collected before the start of therapy and at months 3, 6, 9, 12, 18, 24 and 30 respectively. Subsequently, MRD analyses will be performed every 6 months until clinical progression of the disease or for a maximum of 4 years (until the end of the study).
If MRD assessment on peripheral blood samples turns from positive to negative within the first 30 months, confirmatory blood and bone marrow samples should be taken 6 months thereafter.
In patients remaining MRD positive at 30 months without clinical progression, single agent ibrutinib therapy is continued for another 12 months.
An independent Data Monitoring Committee (DMC) will be formed and constituted. The independent DMC will review the safety of the treatment and make recommendations as to the further conduct of the study.
The data generated by this phase II study should serve as the basis for a subsequent randomized phase III study comparing the chemotherapy-free combination of ibrutinib plus obinutuzumab with standard immune-chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib and GA 101 | Experimental | Drug: Ibrutinib, Drug: GA 101Initial 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
Key exclusion criteria (28 listed)
- - 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: ImbruvicaIbrutinib (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. | Drug | Ibrutinib and GA 101 |
| GA 101Also: ObinutuzumabObinutuzumab (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. | Drug | Ibrutinib and GA 101 |
Primary outcome
Progression free survival
Time frame: one year progress 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.
14 secondary outcomes
three-year-PFS
Time frame: three years after start of therapy
CR
Time frame: one year after start of therapy and at 30 months after end of maintenance
PR
Time frame: one year after start of therapy and at 30 months after end of maintenance
SD
Time frame: one year after start of therapy and at 30 months after end of maintenance
Duration of response
Time frame: 4,5 up to 6,5 years through study completion
Percentage of Progression
Time frame: 4,5 up to 6,5 years through study completion
TTF after start of therapy
Time frame: 4,5 up to 6,5 years through study completion
Time to next anti-lymphoma therapy / time to next chemotherapy based treatment
Time frame: 4,5 up to 6,5 years through study completion
Treatment associated adverse events
Time frame: 4,5 up to 6,5 years through study completion
Percentage of MRD negative patients during therapy
Time frame: 4,5 up to 6,5 years through study completion
Duration of molecular remission
Time frame: 4,5 up to 6,5 years through study completion
Percentage of secondary transformation
Time frame: 4,5 up to 6,5 years through study completion
Percentage of secondary malignancies
Time frame: 4,5 up to 6,5 years through study completion
Time to first secondary malignancy
Time frame: 4,5 up to 6,5 years through study completion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wolfgang Hiddemann, Prof. principal investigator
LMU Klinikum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib and GA 101 in people with Indolent Non-Hodgkin Lymphoma, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: one year progress free survival). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2021.