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An Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion in Patients With Previously Untreated Advanced Follicular Lymphoma

NCT03817853

Description:

This open-label, single arm study will evaluate the safety of obinutuzumab administered as a short duration infusion (SDI; target 90-minute infusion) during cycle 2 and from cycle 2 onwards in combination with chemotherapy in participants with previously untreated advanced follicular lymphoma (FL). The study has two phases: in the first phase, participants will receive the first cycle of obinutuzumab-based chemotherapy (G-chemo) induction therapy as usual with the first three infusions of obinutuzumab (1000 mg) administered at the regular infusion rate on Day 1, 8, and 15 of cycle 1. Phase 2 starts when participants who do not experience any Grade ≥ 3 infusion related reactions during the first cycle receive their first obintuzumab infusion given at the faster infusion rate in Cycle 2. For Cycle 2, Day 1 and all other following infusions (including maintenance), obinutuzumab will be administered at a faster infusion of 90-minute SDI, as long as the participant does not experience any Grade ≥ 3 infusion related reactions. The investigator is free to choose the chemotherapy for each participant (bendamustine, CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone/methylprednisolone], or CVP [cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone]). The total number of cycles of G-chemo induction therapy and the cycles length depends on the chemotherapy chosen for each participant.

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 4

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion in Patients With Previously Untreated Advanced Follicular Lymphoma
  • Official Title: A Multicentric, Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion (SDI) in Patients With Previously Untreated Advanced Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: MO40597
  • NCT ID: NCT03817853

Conditions

  • Advanced Follicular Lymphoma

Interventions

DrugSynonymsArms
ObinutuzumabGA101, RO5072759Obinutuzumab+Chemotherapy
BendamustineObinutuzumab+Chemotherapy
CyclophosphamideObinutuzumab+Chemotherapy
DoxorubicinObinutuzumab+Chemotherapy
Prednisone/Prednisolone/MethylprednisoloneObinutuzumab+Chemotherapy
VincristineObinutuzumab+Chemotherapy

Purpose

This open-label, single arm study will evaluate the safety of obinutuzumab administered as a short duration infusion (SDI; target 90-minute infusion) during cycle 2 and from cycle 2 onwards in combination with chemotherapy in participants with previously untreated advanced follicular lymphoma (FL). The study has two phases: in the first phase, participants will receive the first cycle of obinutuzumab-based chemotherapy (G-chemo) induction therapy as usual with the first three infusions of obinutuzumab (1000 mg) administered at the regular infusion rate on Day 1, 8, and 15 of cycle 1. Phase 2 starts when participants who do not experience any Grade ≥ 3 infusion related reactions during the first cycle receive their first obintuzumab infusion given at the faster infusion rate in Cycle 2. For Cycle 2, Day 1 and all other following infusions (including maintenance), obinutuzumab will be administered at a faster infusion of 90-minute SDI, as long as the participant does not experience any Grade ≥ 3 infusion related reactions. The investigator is free to choose the chemotherapy for each participant (bendamustine, CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone/methylprednisolone], or CVP [cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone]). The total number of cycles of G-chemo induction therapy and the cycles length depends on the chemotherapy chosen for each participant.

Trial Arms

NameTypeDescriptionInterventions
Obinutuzumab+ChemotherapyExperimentalParticipants received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. The investigator is free to choose the chemotherapy for each patient.
  • Obinutuzumab
  • Bendamustine
  • Cyclophosphamide
  • Doxorubicin
  • Prednisone/Prednisolone/Methylprednisolone
  • Vincristine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with previously untreated Stage III or IV FL or Stage II bulky disease
             scheduled to receive obinutuzumab plus chemotherapy due to at least one of the
             following criteria: a.) Bulky disease, defined as a nodal or extranodal (except
             spleen) mass

             ≥ 7 cm in the greatest diameter b.) Local symptoms or compromise of normal organ
             function due to progressive nodal disease or extranodal tumor mass c.) Presence of B
             symptoms (fever [> 38ºC], drenching night sweats, or unintentional weight loss of >
             10% of normal body weight over a period of 6 months or less) d.) Presence of
             symptomatic extranodal disease (e.g., pleural effusions, peritoneal ascites) e.)
             Cytopenias due to underlying lymphoma (i.e., absolute neutrophil count < 1.0 × 109/L,
             hemoglobin < 10 g/dL, and/or platelet count < 100 × 109/L) f.) Involvement of ≥ 3
             nodal sites, each with a diameter of ≥ 3 cm g.) Symptomatic splenic enlargement

          -  Histologically documented CD-20-positive FL, as determined by the local laboratory

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0−2

          -  Adequate hematologic function (unless abnormalities are related to FL)

          -  Life expectancy of ≥ 12 months

          -  For women who are not postmenopausal (≥ 12 consecutive months of non-therapy-induced
             amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to
             remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
             that result in a failure rate of < 1% per year during the treatment period and for at
             least 18 months after the last dose of obinutuzumab, for at least 3 months after the
             last dose of bendamustine or according to institutional guidelines for CHOP or CVP
             chemotherapy, whichever is longer

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures and agreement to refrain from donating sperm

        Exclusion Criteria:

          -  Relapsed / refractory FL

          -  Prior treatment for FL with chemotherapy, radiotherapy, or immunotherapy

          -  Grade IIIb FL

          -  Histological evidence of transformation of FL into high-grade B-cell NHL

          -  Treatment with systemic immunosuppressive medications, including, but not limited to,
             prednisone/prednisolone/methylprednisolone, azathioprine, methotrexate, thalidomide,
             and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1

          -  History of solid organ transplantation

          -  History of anti-CD20 antibody therapy

          -  History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine
             monoclonal antibodies

          -  Known sensitivity or allergy to murine products

          -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
             or any of the study drugs

          -  Active bacterial, viral, fungal, or other infection or any major episode of infection
             requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1

          -  Positive test results for chronic HBV infection (defined as positive HBsAg serology)

          -  Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology
             testing)

          -  Known history of HIV positive status

          -  History of progressive multifocal leukoencephalopathy (PML)

          -  Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1 or
             anticipation that such a live, attenuated vaccine will be required during the study

          -  History of prior other malignancy with the exception of: a. Curatively treated
             carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the
             breast, basal- or squamous-cell skin cancer, Stage I melanoma, or low-grade,
             early-stage localized prostate cancer b. Any previously treated malignancy that has
             been in remission without treatment for ≥ 2 years prior to enrollment

          -  Evidence of any significant, uncontrolled concomitant disease that could affect
             compliance with the protocol or interpretation of results, including significant
             cardiovascular disease (such as New York Heart Association Class III or IV cardiac
             disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or
             unstable angina) or significant pulmonary disease (such as obstructive pulmonary
             disease or history of bronchospasm)

          -  Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of
             Cycle 1, Day 1, or anticipation of a major surgical procedure during the course of the
             study

          -  Any of the following abnormal laboratory values:

               1. Creatinine > 1.5 × the upper limit of normal (ULN) (unless creatinine clearance
                  normal) or creatinine clearance < 40 mL/min

               2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN

               3. Total bilirubin ≥ 1.5 × the ULN: Patients with documented Gilbert disease may be
                  enrolled if total bilirubin is ≤ 3.0 × the ULN.

               4. International normalized ratio (INR) > 1.5 in the absence of therapeutic
                  anticoagulation

               5. Partial thromboplastin time or activated partial thromboplastin time > 1.5 × ULN
                  in the absence of a lupus anticoagulant

          -  For patients who will be receiving CHOP: left ventricular ejection fraction (LVEF) <
             50% by multigated acquisition (MUGA) scan or echocardiogram

          -  Pregnant or lactating, or intending to become pregnant during the study

          -  Any investigational therapy within 28 days prior to the start of Cycle 1
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Grade ≥3 Infusion-Related Reactions (IRRs) During Cycle 2 in Patients Who Had Previously Received Obinutuzumab at the Standard Infusion Rate During Cycle 1 Without Experiencing a Grade 3 or 4 IRR
Time Frame:Within 24 hours from the end of study treatment infusion of Day 1 in Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants With Adverse Events (AEs)
Time Frame:Baseline up to end of study (up to approximately 4 years)
Safety Issue:
Description:
Measure:Percentage of IRRs Regardless of Grade by Cycle
Time Frame:Within 24 hours from the end of study treatment infusion in all cycles, including maintenance ((1 cycle: 21 or 28 days depending on the chemotherapy selected); up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Time to IRR From Infusion to Onset of the IRR During Cycle 2
Time Frame:From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
Safety Issue:
Description:
Measure:Duration (In Minutes) of Obinutuzumab Administration by Cycle
Time Frame:All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Duration of Grade ≥3 IRRs Associated with the obinutuzumab Administered as an SDI by Cycle
Time Frame:All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Overall Response Rate at the End of Induction Therapy
Time Frame:Baseline up to end of induction therapy (up to approximately 6 months)
Safety Issue:
Description:
Measure:Progression-Free Survival Rate at the End of the Study
Time Frame:Baseline up to end of study (up to approximately 4 years)
Safety Issue:
Description:
Measure:Overall Survival at the End of the Study
Time Frame:Baseline up to end of study (up to approximately 4 years)
Safety Issue:
Description:
Measure:Complete Response (CR) Rate at 30 Months (CR30), as Assessed by the Investigator and According to the Guidelines Used at the Site
Time Frame:Baseline up to 30 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

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