Study of Atezolizumab Plus BEGEV Regimen in Relapsed or Refractory Hodgkin's Lymphoma Patients
NCT ID: NCT05300282
Last Updated: 2025-08-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
122 participants
INTERVENTIONAL
2023-02-27
2030-04-27
Brief Summary
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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. arm A will receive the BEGEV regimen followed by ASCT for patients achieving CR.
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.
After the last treatment date of the last patient (LPLT), the phase IIb will be ended. A long term follow up will start, in order to better assess patients' prognosis. All evaluable patients from phase I and phase IIb study will enter in the long term follow up phase and will be followed for 18 months.
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Detailed Description
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6-18 patients enrolled in this phase 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.
Patients with documented CR following ASCT will receive a consolidation therapy with atezolizumab as single agent every 4 weeks for 6 doses, starting preferably between 60 and 90 days, but ≥ 60 days and not \> 120 days after autografting. In patients not previously radiotreated, adjuvant radiotherapy (RT) should be planned during consolidation treatment within the start of second consolidation dose, according to clinician's judgment and response assessment. RT will be administered at 30-36 Gy on sites of initial bulky disease or on single PET positive residual site.
Patients reaching PR after four cycles of atezolizumab combined with BEGEV or with documented PR after ASCT may continue the study protocol according to the physician judgment.
Dosing starts at 1200 mg and decreases in the successive cohort to the dose of 840 mg and 600 mg, according to Flow chart A. in the section 6 of the protocol.
In the consolidation phase atezolizumab will be administered at dose of 1200 mg every 4 weeks for 6 doses without dose reduction, but only delay or discontinuation.
Patients included in the cohort developing DLT, withdraw the protocol due to toxicity and continue the treatment according to good clinical practice.
For patients included in the cohort of MTD, monitoring and collection of AEs will be continuous during induction, consolidation treatment and follow-up.
The phase IIb part (expansion cohort) plans to randomize 122 patients in two arms (A and B, 61 per arm):
1. arm A will receive the BEGEV regimen followed by ASCT for patients achieving CR.
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.
In patients not previously radiotreated, adjuvant RT should be planned for both patients in arm A and arm B according to clinician's judgment and response assessment. RT will be administered at 30-36 Gy on sites of initial bulky disease or on single PET positive residual site.
Patients reaching PR after four induction cycles (atezolizumab combined with BEGEV or BEGEV alone) or with documented PR after ASCT may continue the study protocol according to the physician judgment.
After the last treatment date of the last patient (LPLT), the phase IIb will be ended. A long term follow up will start, in order to better assess patients' prognosis. All evaluable patients from phase I and phase IIb study will enter in the long term follow up phase and will be followed for 18 months. Disease status, survival outcome, secondary primary malignancies and late toxicity will be collected every 6 months until patient withdrawal of consent, lost to follow up and patient's death. Long term follow-up phase will end 18 months after the end of phase IIb.
Conditions
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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phase I
patients will receive the BEGEV regimen plus Atezolizumab in order to determine MTD of the last one drug.
Atezolizumab
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).
BEGEV
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.
phase IIb - arm A
patients will receive the BEGEV regimen followed by ASCT for patients achieving CR.
BEGEV
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.
phase IIb - arm B
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.
Atezolizumab
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).
BEGEV
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.
Interventions
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Atezolizumab
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).
BEGEV
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
Exclusion Criteria
* 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 positive with HBV DNA \< 2000 UI/ml (inactive carriers); HBV DNA \> 2000 UI/ml is criteria of exclusion
* 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.
* Prior history of malignancies, other than HL, unless the patient has been free for at least 5 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) \> 3 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.
* Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
* Pregnancy or breastfeeding, or unwillingness to comply with adequate contraception (one negative pregnancy test within 14 days prior to initiation of study treatment required).
* 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.
Exception to Exclusion:
* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
* Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
* Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease (COPD) exacerbation) are eligible for the study.
18 Years
60 Years
ALL
No
Sponsors
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Roche Pharma AG
INDUSTRY
Fondazione Italiana Linfomi - ETS
OTHER
Responsible Party
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Principal Investigators
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Armando Santoro, MD
Role: PRINCIPAL_INVESTIGATOR
U.O. Ematologia - Istituto Clinico Humanitas - Rozzano - ITALY
Locations
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S.C. Ematologia - A.O. SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Alessandria, Italy
Ematologia - Fondazione del Piemonte per l'Oncologia - IRCCS
Candiolo, Turin, Italy
S.C. Ematologia e Trapianto emopoietico - Azienda Ospedaliera S.Giuseppe Moscati
Avellino, , Italy
Divisione di Oncologia e dei Tumori immuto-correlati - IRCCS Centro di Riferimento Oncologico di Aviano
Aviano, , Italy
U.O.C Ematologia - IRCCS Istituto Tumori Giovanni Paolo II
Bari, , Italy
Ematologia - Ospedale "Monsignor Raffaele Dimiccoli"
Barletta, , Italy
Ematologia - ASST Spedali Civili di Brescia
Brescia, , Italy
Ematologia - Ospedale Vito Fazzi
Lecce, , Italy
Ematologia - Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milan, , Italy
SC Ematologia - ASST Grande Ospedale Metropolitano Niguarda
Milan, , Italy
U.O. Onco-ematologia - Presidio ospedaliero "A. TORTORA"
Pagani, , Italy
Divisione di Ematologia - A.O. Ospedali Riuniti Villa Sofia-Cervello
Palermo, , Italy
Div. di Ematologia - IRCCS Policlinico S. Matteo di Pavia
Pavia, , Italy
Ematologia - Ospedale S. Maria della Misericordia
Perugia, , Italy
Ematologia - Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova
Reggio Emilia, , Italy
Ematologia - Ospedale S. Camillo
Roma, , Italy
Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione - Policlinico Umberto I - Università "La Sapienza"
Roma, , Italy
Policlinico Universitario Campus Bio-Medico - Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare
Roma, , Italy
U.O. Ematologia - Istituto Clinico Humanitas
Rozzano, , Italy
S.C. Oncoematologia - A.O. S. Maria di Terni
Terni, , Italy
S.C.Ematologia - A.O.U. Città della Salute e della Scienza di Torino
Torino, , Italy
Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia
Trieste, , Italy
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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FIL_A-BEGEV
Identifier Type: -
Identifier Source: org_study_id
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