Idelalisib+Obinutuzumab in Patients With Relapsed/Refractory Follicular Lymphoma (GAUDEALIS)

Idelalisib Plus Obinutuzumab in Patients With Relapsed/Refractory Follicular Lymphoma: a Phase 2, Single-arm, Multicentric Study

Single arm, prospective, multi-centric, phase II study. Patients with histologically confirmed follicular lymphoma, in need of a systemic approach and failing (i.e. with refractory disease [no response or response lasting less than 6 months at any previous line of treatment] or with a proven disease relapse) at least 2 previous lines of treatment, including any antibody directed against the CD20 antigen-containing chemotherapy, will undergo a combined chemo-free treatment with obinutuzumab and idelalisib.

Study Overview

• Status: Terminated
• Conditions: Follicular Lymphoma
• Intervention / Treatment: Drug: Idelalisib; Drug: Obinutuzumab

Detailed Description

Single arm, prospective, multi-centric, phase II study. Patients with histologically confirmed follicular lymphoma, in need of a systemic approach and failing (i.e. with refractory disease [no response or response lasting less than 6 months at any previous line of treatment] or with a proven disease relapse) at least 2 previous lines of treatment, including any antibody directed against the CD20 antigen-containing chemotherapy, will undergo a combined chemo-free treatment with obinutuzumab and idelalisib.

Obinutuzumab will be administered intravenously at a flat dose of 1000 mg on day 1, 8, 15 of the first cycle, then repeated on day 1 of each subsequent cycle, for 6 cycles (each cycle is completed in 28 days). Idelalisib will be given concomitantly with obinutuzumab and on a daily 150 mg bid schedule. For patients achieving at least a partial response at the end of induction, a maintenance phase with obinutuzumab is scheduled (on day 1 every two months for two years or until progression or unacceptable toxicity, whichever comes first) If one of the two drugs has to be permanently discontinued due to any cause, patient may continue treatment with the other agent if it is judged to be a clinical benefit. Patients with at least a stable disease will enter the follow-up phase and will be followed with repeated CT scans every six months for two years or until death/progression occurs (whichever comes firsts).

Patients with progressive disease, whenever progression is documented, will enter a survival follow up period of two years after PD was documented. These patients are however considered evaluable for OS.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Policlinico S.Orsola-Malpighi - Istituto di Ematologia "Seragnoli"
  • Firenze, Italy, 50141
    • Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
  • Novara, Italy, 28100
    • AOU Maggiore della Carità di Novara - SCDU Ematologia
  • Trieste, Italy, 34121
    • Azienda sanitaria-universitaria integrata Trieste (ASUITS) - SC Ematologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

Relapsed or refractory, histologically confirmed CD20-positive follicular non-Hodgkin's lymphoma, grade 1, 2 or 3a according to WHO 2017 classification.

• Age 18 ≥ years
• At least 2 prior systemic therapies for follicular lymphoma including both any antibody directed against the CD20 antigen and a chemotherapy combination.

• Treatment indications, with the presence of at least one of the following:

  • bulky disease (nodal or extranodal mass - except spleen -more than 7 cm in its greater diameter or involvement of at least 3 nodal or extranodal sites, each with a diameter equal to or greater than 3 cm);
  • at least one B-symptom (fever > 38°C of unclear etiology, night sweats, weight loss greater than 10% of body weight in the prior 6 months);
  • symptomatic splenomegaly;
  • compression syndrome (i.e. of orbits, ureters, gastrointestinal tract, biliary tract);
  • lymphoma-related cytopenias (hemoglobin < 10 g/dL and/or platelets < 100.000/mmc and/or neutrophils < 1.500/mmc);
  • pleural or peritoneal serous effusions;
  • lactate dehydrogenase elevation.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
• Adequate hematological function, unless abnormalities due to underlying disease, within 28 days prior to signing informed consent, defined as follows: neutrophils > 1.500/mmc, platelets > 75.000/mmc, hemoglobin > 8,0 g/dL with transfusion independence.
• Capacity and willingness to adhere to study visit schedule and specific protocol procedures.
• Willingness to sign a written informed consent.
• Compliance with effective contraception without interruption, from 28 days before treatment start up (i.e., during the screening phase) to 18 months after treatment discontinuation, agreeing not to donate the semen during treatment and for 18 months after discontinuation (if the patient is male), or to undergo ongoing pregnancy test during the course of the study (if the patient is female).
• Patients must agree to undergo JPJ prophylaxis throughout the treatment period and 2-6 months thereafter (before consulting with Medical Monitor).

Exclusion criteria

Grade 3b follicular non-Hodgkin's lymphoma or evidence of transformation to high-grade non-Hodgkin's lymphoma.

• Central nervous system or leptomeningeal involvement by lymphoma.
• Major surgery (excluding any lymph node biopsy) within 28 days prior to signing informed consent.
• Seropositivity for HBV or evidence of active infection (HBsAg positivity, or HBsAg negativity with positive anti-HBs/anti-HBc and detectable viral DNA load); if viral load is negative or undetectable, the patient is eligible, provided their HBsAg negativity.
• Positive viral HCV RNA
• Seropositivity for HIV, regardless of viral load.
• Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension
• Known history of drug induced pneumonitis
• On-going inflammatory bowel disease
• On-going alcohol or drug addiction
• Life expectancy lower than 6 months.
• Prior history of malignancies, other than follicular lymphoma, unless the patient has been free for at least 10 years (exceptions: localized non-melanoma skin cancer ad carcinoma in situ of the cervix).
• Any of the following laboratory abnormalities: liver enzymes (AST/SGOT and/or ALT/SGPT) > 2.5-fold the upper limit of normal (except of liver involvement by lymphoma); total bilirubin > 1.5 mg/dL (except for patients with known Gilbert's disease or biliary tree compression by lymphoma masses); creatinine clearance < 30 mL/min.
• Uncontrolled intercurrent illness.
• Known hypersensitivity or allergy to murine products or to any of the medicaments under investigation.
• Pregnancy or breastfeeding, or unwillingness to comply with adequate contraception.
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent the patient from signing the informed consent or which may place the patient at unacceptable risk if participating in the study.
• Any evidence of ongoing bacterial, viral and fungal infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idelalisib Plus Obinutuzumab; Single arm: Regimen: GAUDEALIS q28 days; Obinutuzumab Dose: 1000 mg IV Day 1, 8, 15 (1st cycle); Obinutuzumab Dose: 1000 mg IV Day 1 (2nd cycle onward); Idelalisib Dose: 150 mg BID oral Daily (24 weeks)	Drug: Idelalisib; Idelalisib Plus Obinutuzumab In Patients With Relapsed/Refractory Follicular Lymphoma; Drug: Obinutuzumab; Idelalisib Plus Obinutuzumab In Patients With Relapsed/Refractory Follicular Lymphoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint - Overall response rate (ORR)	Investigator's assessed Overall response rate at the end of induction phase of patients treated with a chemo-free combination with obinutuzumab and idelalisib. Overall response rate is defined as the proportion of patients with at least a partial response	through the completion of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoints 1 - Overall survival (OS) rate	Overall survival rate	at the end of induction phase of patients treated with a chemo-free. Through the completion of the study
Secondary Endpoints 2 - Progression-free survival (PFS) rate	Progression-free survival rate	at the end of induction phase of patients treated with a chemo-free. Through the completion of the study
Secondary Endpoints 3 - patients' withdrawal rate	patients' withdrawal rate, incidence and nature of any severe adverse events hospitalization rate throughout the study, and patients' compliance to oral treatment, incidence of any adverse events occurring during and right after treatment	at the end of induction phase of patients treated with a chemo-free. Through the completion of the study

Collaborators and Investigators

• Sponsor: Fondazione Italiana Linfomi - ETS
• Investigators: Principal Investigator: Pierluigi Zinzani, Prof., Bologna - Policlinico S.Orsola-Malpighi - Istituto di Ematologia "Seragnoli"

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2019
• Primary Completion (Actual): April 29, 2021
• Study Completion (Actual): May 10, 2023

Study Registration Dates

• First Submitted: March 21, 2019
• First Submitted That Met QC Criteria: March 22, 2019
• First Posted (Actual): March 26, 2019

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Obinutuzumab; Idelalisib; Relapsed/Refractory Follicular Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Obinutuzumab; Idelalisib
• Other Study ID Numbers: FIL_GAUDEALIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No