Clinical trial NCT03817853: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Advanced Follicular Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-01-28
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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 (at a dose equivalent to \>30 mg/day prednisone), 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
* Positive test results for human T-lymphotropic virus 1 (HTLV-1)

Primary outcomes:
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
timeFrame: 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)
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to end of study (approximately 4 years)
measure: Percentage of IRRs Regardless of Grade by Cycle
timeFrame: 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)
measure: Time to IRR From Infusion to Onset of the IRR During Cycle 2
timeFrame: From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
measure: Duration (In Minutes) of Obinutuzumab Administration by Cycle
timeFrame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
measure: Type of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle
timeFrame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
measure: Duration of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle
timeFrame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
measure: Objective Response Rate (ORR) at the End of Induction (EOI) Therapy
timeFrame: Baseline up to end of induction therapy (up to approximately 6 months)
measure: Progression-Free Survival (PFS) Rate at the End of the Study
timeFrame: Baseline up to end of study (up to approximately 4 years)
measure: Overall Survival (OS) at the End of the Study
timeFrame: Baseline up to end of study (up to approximately 4 years)
measure: Complete Response (CR) Rate at 30 Months (CR30), as Assessed by the Investigator and According to the Guidelines Used at the Site
timeFrame: Baseline up to 30 months
Other outcomes:
Locations:
city: Boulder
country: United States
facility: Rocky Mountain Cancer Center; Medical Oncology
state: Colorado
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: Florham Park
country: United States
facility: Summit Medical Center
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Eugene
country: United States
facility: Willamette Valley Cancer Ctr - 520 Country Club
state: Oregon
city: Austin
country: United States
facility: Texas Onc-Central Austin CA Ct
state: Texas
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Fortaleza
country: Brazil
facility: NOHC - Núcleo de Oncologia e Hematologia do Ceará
state: CE
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: RS
city: Jau
country: Brazil
facility: Hospital Amaral Carvalho
state: SP
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Hämatologie und Onkologie
city: Dessau-Roßlau
country: Germany
facility: Städtisches Klinikum Dessau
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt; Medizinische Klinik II; Onkologie
city: Hamburg
country: Germany
facility: OncoResearch Lerchenfeld GmbH
city: Köln
country: Germany
facility: Klinik der Uni zu Köln; I. Med. Klinik
city: Landshut
country: Germany
facility: MVZ Dr. Vehling-Kaiser GmbH; Onkologische Praxis
city: Lübeck
country: Germany
facility: Onkologische Schwerpunktpraxis Lübeck
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Hyogo
country: Japan
facility: Kobe City Medical Center General Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis - loc Dordrecht
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Vitoria
country: Spain
facility: Hospital De Txagorritxu; Servicio de Hematologia
state: Alava
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar; Servicio de Hematologia
state: Cadiz
city: Barcelona
country: Spain
facility: Hospital del Mar; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario la Paz; Servicio de Hematologia
city: Murcia
country: Spain
facility: Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: