A Phase Ib/II study evaluating the safety, tolerability and anti-tumor activity of polatuzumab vedotin in combination with rituximab (R) or obinutuzumab (G) plus bendamustine (B) in relapsed or refractory follicular or diffuse large B-cell lymphoma
- Conditions
- disease of white bloodcellsNon-Hodgkin Lymphoma10025320
- Registration Number
- NL-OMON47634
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
- Age * 18 years
- Histologically confirmed FL (Grade 1, 2, or 3a) or DLBCL
- Must have received at least one prior therapy for FL or DLBCL. Patients must
have either relapsed or have become refractory to a prior regimen as defined in
the protocol.
- If the patient has received prior bendamustine, response duration must have
been > 1 year (for patients who have relapse disease after a prior regimen)
- At least one bi-dimensionally measurable lesion on imaging scan defined as >
1.5 cm in its longest dimension
- Confirmed availability of archival or freshly collected tumor tissue prior
to study enrollment
- Life expectancy of at least 24 weeks
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Adequate hematologic function unless inadequate function is due to
underlying disease.
- For women who are not postmenopausal (* 12 months of non*therapy*induced
amenorrhea and age > 45 years) or surgically sterile: agreement to remain
abstinent or to use single highly effective or combined contraceptive methods
that result in a failure rate of < 1% per year during the treatment period and
for * 12 months after the last dose of rituximab or for * 18 months after the
last dose of obinutuzumab, and agreement to refrain from donating eggs.
- For women of childbearing potential, a negative serum pregnancy test result
within 7 days prior to commencement of dosing.
- For men, agreement to remain abstinent or to use a condom plus an additional
contraceptive method that together result in a failure rate of < 1% per year
during the treatment period and for at least 6 months after the last dose of
study drug and agreement to refrain from donating sperm during this same period
- History of severe allergic or anaphylactic reactions to humanized or murine
MAbs (or recombinant antibody-related fusion proteins) or known sensitivity or
allergy to murine products
- Contraindication to bendamustine, rituximab, or obinutuzumab
- History of sensitivity to mannitol (mannitol is an excipient in bendamustine)
- Prior use of any MAb, radioimmunoconjugate, or ADC within 5 half-lives or 4
weeks, whichever is longer before Cycle 1 Day 1
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive
therapy, or any investigational agent for the purposes of treating cancer
within 2 weeks prior to Cycle 1 Day 1
- Ongoing corticosteroid use > 30 mg/day prednisone or equivalent, for
purposes other than lymphoma symptom control
- Treatment with chimeric antigen receptor T-cell therapy within 100 days prior
to Cycle 1 Day 1
- Completion of autologous stem cell transplant within 100 days prior to Cycle
1 Day 1
- Prior allogeneic stem cell transplant
- Eligibility for autologous SCT
- Grade 3b follicular lymphoma
- History of transformation of indolent disease to DLBCL
- Primary or secondary CNS lymphoma
- Current Grade > 1 peripheral neuropathy
- History of other malignancy that could affect compliance with the protocol
or interpretation of results.
- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results, including
significant cardiovascular disease or significant pulmonary disease
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other
infection at study enrollment or any major episode of infection requiring
treatment with intravenous (IV) antibiotics or hospitalization within 4 weeks
prior to Cycle 1 Day 1
- Patients with suspected or latent tuberculosis,
- Positive test results for chronic hepatitis B virus infection or for
hepatitis C virus antibody
- Known history of HIV seropositive status
- Known infection of human T-cell leukemia virus 1 virus
- Vaccination with a live vaccine within 28 days prior to treatment
- Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1)
other than for diagnosis
- Women who are pregnant or lactating or who intend to become pregnant within
a year of the last dose of study treatment in the rituximab cohorts or within
18 months of the last dose of study treatment in the obinutuzumab cohort
- Any abnormal laboratory values as defined in the protocol, unless abnormal
laboratory values are due to underlying lymphoma per the investigator
- Any other diseases, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or
condition that contraindicates the use of an investigational drug or that may
affect the interpretation of the results or render the patient at high risk
from treatment complications
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy Outcome Measures:<br /><br><br /><br>Response assessment will be determined according to Modified Lugano Response<br /><br>Criteria for Malignant Lymphoma (Lugano Classification; Cheson et al. 2014; see<br /><br>Appendix 4 in the protocol).<br /><br>* CR at primary response assessment (6*8 weeks after Cycle 6, Day 1, or last<br /><br>dose of study drug) based on PET/CT, as determined by the investigator and IRC<br /><br>* OR (CR or PR) at primary response assessment based on PET/CT, as determined<br /><br>by the investigator and IRC<br /><br>* CR at primary response assessment based on CT only, as determined by the<br /><br>investigator and IRC<br /><br>* OR (CR or PR) at primary response assessment based on CT only, as determined<br /><br>by the investigator and IRC<br /><br>* BOR (CR or PR) while on study based on PET/CT or CT only, as determined by<br /><br>the investigator<br /><br>* NF cohort only: OS and EFS based on PET-CT or CT only, as determined by the<br /><br>investigator</p><br>
- Secondary Outcome Measures
Name Time Method