Study of Atezolizumab Plus BEGEV Regimen in Relapsed or Refractory Hodgkin's Lymphoma Patients

NCT05300282 | Recruiting Phase 1 DMC

• 1 other identifier: FIL_A-BEGEV
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 32

Brief Summary

The phase I part (safety assessment of the combination treatment) is aimed at determining the MTD of atezolizumab when combined with BEGEV schedule. 6-18 patients enrolled in this part will be treated with atezolizumab in combination with BEGEV regimen every 3 weeks for 4 cycles. Patients without a DLT in the first cycle and without disease progression after cycle 2, will undergo stem cell mobilization with 3-4 cycle of A-BEGEV + granulocyte colony-stimulating factor (G-CSF) and subsequently receive a myeloablative therapy followed by ASCT. The phase IIb part (expansion cohort) plans to randomize 122 patients in two arms (A and B, 61 per arm):

1. 1.arm A will receive the BEGEV regimen followed by ASCT for patients achieving CR.
2. 2.arm B will receive combination treatment with Atezolizumab and BEGEV regimen followed for patients reaching CR by ASCT plus a consolidation with 6 doses of atezolizumab at 1200 mg every 4 weeks.

Conditions

Relapsed or Refractory Hodgkin's Lymphoma

Keywords

Hodgkin's lymphoma; atezolizumab; BEGEV; phase I/II b study; relapsed; refractory; MTD

Outcome Measures

Primary Outcomes (2)

• For Phase I part: evaluation of the maximum tolerated dose (MTD) of the atezolizumab.

  The maximum tolerated dose (MTD) of the atezolizumab in combination with BEGEV will be established in the first cycle of therapy, in order to determine the recommended phase II dose (RP2D). Patients will be accrued in 3 patients cohorts at each dose level, starting from level 1. Dose de-escalation will be performed following the standard 3+3 rule, registering any Dose Limiting Toxicity (DLT).

  During first cycle of treatment based on atezolizumab in combination with BEGEV in phase I study. Maximum time frame 17 months.

• For Phase II part: evaluation of the Complete Response Rate (CRR) before ASCT.

  The assessment of CRR before ASCT will be performed by an independent radiologic review committee (IRRC) according to the Lugano classification response criteria (2014) and the LYmphoma Response to Immunomodulatory Therapy Criteria (LYRIC 2016). CRR will be defined as the proportion of patients in CR after the first 4 cycles of induction treatment, according to Lugano classification response Criteria and LYRIC 2016 criteria. Patients without response assessment (due to whatever reason) will be considered as non-responders.

  From initial treatment based on Atezolizumab and BEGEV to intensification treatment with ASCT. Time frame 4 months.

Secondary Outcomes (9)

• For Phase II part: evaluation of the overall response rate (ORR), partial response (PR), stable disease (SD) and progression disease (PD) rates.

  The best response between the date of beginning of therapy and the last restaging. Time frame 14 months.

• For Phase II part: evaluation of the rate of partial response (PR) converted to Complete Response (CR).

  At the end of consolidation treatment with atezolizumab in the experimental arm. Time Frame 14 months.

• For Phase II part: evaluation of the peripheral blood stem-cell mobilization

  At the end of treatment based on atezolizumab and BEGEV. Time Frame 3 months.

• For Phase II part: evaluation of engraftment after ASCT

  Between 30 and 60 days after ASCT: Time Frame 5 months.

• For Phase II part: evaluation of duration of response (DoR).

  From the CR to the date of relapse or progression or last scheduled visit. Time frame 50 months.

Study Arms (3)

phase I

EXPERIMENTAL

patients will receive the BEGEV regimen plus Atezolizumab in order to determine MTD of the last one drug.

Drug: Atezolizumab; Combination Product: BEGEV

phase IIb - arm A

ACTIVE COMPARATOR

patients will receive the BEGEV regimen followed by ASCT for patients achieving CR.

Combination Product: BEGEV

phase IIb - arm B

EXPERIMENTAL

patients will receive combination treatment with Atezolizumab (at dose obtained from phase I) and BEGEV regimen followed for patients reaching CR by ASCT plus a consolidation with 6 doses of atezolizumab at 1200 mg every 4 weeks.

Drug: Atezolizumab; Combination Product: BEGEV

Interventions

Atezolizumab DRUG

In phase I study: Atezolizumab will be administered until the determination of its MTD when combined with BEGEV schedule. In phase II b study - arm A (standard): Atezolizumab will not be administered. In phase II b study - arm B (experimental): Atezolizumab will be administered at MTD determined in phase I study plus BEGEV regimen (at dosages performed by local practice).

phase I; phase IIb - arm B

BEGEV COMBINATION_PRODUCT

In phase I study: Atezolizumab will be administered until the determination of its MTD when combined with BEGEV schedule. In phase II b study - arm A (standard): only BEGEV will be administered. In phase II b study - arm B (experimental): BEGEV regimen will be administered in combination with Atezolizumab at MTD determined in phase I.

Also known as: Bendamustine, Gemcitabine, Vinorelbine

phase I; phase IIb - arm A; phase IIb - arm B

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years old (upper limit valid only for phase I).
• Histologically confirmed cHL, at first disease relapse or refractory to a first-line treatment or with documented persistent disease at interim positron emission tomography (PET) performed after 2 cycles of first line (ABVD/ABVD like/BEACOPP).
• Only one prior systemic therapy for Hodgkin's lymphoma (HL).
• First disease relapse or refractory to a first-line treatment.
• Eligibility for ASCT.
• Performance status (PS) ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Adequate haematological function, unless abnormalities due to underlying disease, at the moment of signing informed consent, defined as follows:
• neutrophils \> or = 1.500/mmc and
• platelets \> or = 75.000/mmc and
• haemoglobin \> or = 8,0 g/dL with transfusion independence
• Capacity and willingness to adhere to study visit schedule and specific protocol procedures.
• Compliance with effective contraception without interruption, according to physician's judgement, from 28 days before treatment start up to at least 6 months after treatment discontinuation, agreeing not to donate semen/eggs during treatment and for at least 6 months after last treatment dose.

You may not qualify if:

• More than one prior systemic therapy for HL.
• Presence of autoimmune disease (based on medical history): systemic lupus erythematosus, autoimmune thyroid disease (Hashimoto's thyroiditis, Basedow's disease), Sjögren's syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, idiopathic pulmonary fibrosis (includine bronchiolitis obliterans organizing pneumonia) and inflammatory bowel disease (Crohn's disease, ulcerative colitis).
• Previous skin toxicity (i.e. Steven-Johnson Sdr, severe skin reactions.
• Prior allogeneic stem cell transplantation or prior solid organ transplant.
• History of active tubercolosis.
• History of leptomeningeal disease.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.
• Central nervous system (CNS) 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. The following categories may be considered for the study:
• HBsAg negative but HBsAb positive
• HBsAg negative but HBcAb positive HBsAg positive with HBV DNA \< 2000 UI/ml and HBsAg negative but HBcAb positive will be eligible for the study only if they accept to receive antiviral prophylaxis for all the period of treatment and at least for 12 months after the end of therapy. Treatment should be stopped in case of hepatitis reactivation. - Seropositivity for HCV. Patients with presence of HCV antibody are eligible only if PCR result are negative for HCV RNA
• Seropositivity for HIV.
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail bed) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics except if for tumor fever) within 2 weeks of the start of Cycle 1.
• Life expectancy lower than 6 months.

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead
• Roche Pharma AG: collaborator

Study Sites (32)

S.C. Ematologia - A.O. SS. Antonio e Biagio e Cesare Arrigo

Alessandria, Alessandria, 15121, Italy

RECRUITING

Ematologia - Fondazione del Piemonte per l'Oncologia - IRCCS

Candiolo, Turin, Italy

RECRUITING

S.C. Ematologia e Trapianto emopoietico - Azienda Ospedaliera S.Giuseppe Moscati

Avellino, Italy

RECRUITING

Divisione di Oncologia e dei Tumori immuto-correlati - IRCCS Centro di Riferimento Oncologico di Aviano

Aviano, Italy

RECRUITING

U.O.C Ematologia - IRCCS Istituto Tumori Giovanni Paolo II

Bari, Italy

RECRUITING

Ematologia - Ospedale "Monsignor Raffaele Dimiccoli"

Barletta, Italy

NOT YET RECRUITING

Ematologia - ASST Spedali Civili di Brescia

Brescia, Italy

RECRUITING

Ospedale S. Maria Goretti - UOC Ematologia con Trapianto

Latina, Italy

NOT YET RECRUITING

Ematologia - Ospedale Vito Fazzi

Lecce, Italy

RECRUITING

IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST S.R.L. - Ematologia

Meldola, Italy

NOT YET RECRUITING

Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia

Messina, Italy

RECRUITING

Ematologia - Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Milan, Italy

RECRUITING

SC Ematologia - ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

RECRUITING

Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale - UOC Ematologia Oncologica

Naples, Italy

RECRUITING

U.O. Onco-ematologia - Presidio ospedaliero "A. TORTORA"

Pagani, Italy

RECRUITING

Divisione di Ematologia - A.O. Ospedali Riuniti Villa Sofia-Cervello

Palermo, Italy

RECRUITING

Div. di Ematologia - IRCCS Policlinico S. Matteo di Pavia

Pavia, Italy

RECRUITING

Ematologia - Ospedale S. Maria della Misericordia

Perugia, Italy

RECRUITING

Azienda USL Piacenza - UOC Ematologia e Centro Trapianti

Piacenza, Italy

RECRUITING

Ospedale delle Croci - Ematologia

Ravenna, Italy

RECRUITING

Ematologia - Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova

Reggio Emilia, Italy

RECRUITING

Ospedale degli Infermi di Rimini - U.O. di Ematologia

Rimini, Italy

NOT YET RECRUITING

Ematologia - Ospedale S. Camillo

Roma, Italy

RECRUITING

Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione - Policlinico Umberto I - Università "La Sapienza"

Roma, Italy

RECRUITING

Policlinico Universitario Campus Bio-Medico - Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare

Roma, Italy

RECRUITING

Universitа Cattolica S. Cuore - Ematologia

Roma, Italy

NOT YET RECRUITING

U.O. Ematologia - Istituto Clinico Humanitas

Rozzano, Italy

RECRUITING

S.C. Oncoematologia - A.O. S. Maria di Terni

Terni, Italy

NOT YET RECRUITING

A.O.U. Citta della Salute e della Scienza di Torino - Ematologia Universitaria

Torino, Italy

NOT YET RECRUITING

S.C.Ematologia - A.O.U. Città della Salute e della Scienza di Torino

Torino, Italy

RECRUITING

A.O. C. Panico - U.O.C Ematologia e Trapianto

Tricase, Italy

NOT YET RECRUITING

Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia

Trieste, Italy

RECRUITING

MeSH Terms

Conditions

Recurrence; Hodgkin Disease

Interventions

atezolizumab; Bendamustine Hydrochloride; Gemcitabine; Vinorelbine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Armando Santoro, MD

  U.O. Ematologia - Istituto Clinico Humanitas - Rozzano - ITALY

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Uffici Studi FIL

CONTACT

0131033153; startup@filinf.it

Lorenza Randi, Dr.

CONTACT

0131033153; lrandi@filinf.it

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The phase I part is aimed at determining the MTD of atezolizumab when combined with BEGEV schedule. Atezolizumab dosing starts at 1200 mg and decreases in the successive cohort to the dose of 840 mg and 600 mg to reach MTD which will be used in the phase II part where patients will be randomized in 2 arms: arm A will receive the BEGEV regimen followed by ASCT for patients achieving CR and arm B will receive combination treatment with Atezolizumab and BEGEV regimen followed for patients reaching CR by ASCT plus a consolidation with 6 doses of atezolizumab at 1200 mg every 4 weeks.

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: March 29, 2022
• Study Start: February 27, 2023
• Primary Completion (Estimated): April 27, 2027
• Study Completion (Estimated): April 27, 2030
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (32)