Brentuximab Vedotin in Refractory/Relapsed Hodgkin Lymphoma Treated by ICE

NCT02686346 | Completed Phase 1 DMC

• 1 other identifier: BV-ICE
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 19

Brief Summary

This study is designed as a phase Ib/II trial. The first part (phase Ib) is a dose escalation design to explore the safety and assess the recommended phase 2 dose of Brentuximab Vedotin in Hodgkin lymphoma patients treated with ICE regimen. The second part, depending on the selected dose after the completion of phase Ib part of the study, will further explore safety in addition to efficacy of the recommended dose of Brentuximab Vedotin in a selected population of patients treated with ICE with Hodgkin lymphoma.

Conditions

Hodgkin Disease

Keywords

Relapsed; Refractory

Outcome Measures

Primary Outcomes (2)

• Phase I : Maximal Tolerated Dose (MTD) determination

  To determine the MTD and/or Recommended Phase II dose (RP2D dose) of BV when administered to adult patients treated with ICE in refractory or relapsed Hodgkin's lymphomas.

  4 months

• Phase II = fraction of responding patients according to Lugano classification (metabolic Complete Response)

  To evaluate the efficacy of BV in patient treated with ICE as first salvage treatment (establish the fraction of responding patients - metabolic Complete Response (CR)) as judged by the center by Lugano classification after the second cycle

  2 months

Secondary Outcomes (10)

• Phase I : Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  4 months

• Phase I = Preliminary Overall Response Rate (ORR)

  4 months

• Phase II = ORR

  4 months

• Phase II : Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  4 months

• Phase II = number of patients with hematological recovery after each cycle

  4 months

Study Arms (1)

BV-ICE

EXPERIMENTAL

Phase I: 4 cycles of treatment, every 21 days: Brentuximab Vedotin (BV) + Etoposide- Carboplatine - Ifosfamide (ICE) = BV-ICE for cycles 1 to 3 and BV alone at cycle 4; Phase II: 4 cycles of treatment, every 21 days: BV-ICE for cycles 1 to 3, BV alone at cycle 4

Drug: Brentuximab Vedotin; Drug: Etoposide; Drug: Carboplatine; Drug: Ifosfamide

Interventions

Brentuximab Vedotin DRUG

Phase I: Cohort K: BV on Day 1: 1.2 mg/kg (cycle 1-3) and 1.8 mg/kg (cycle 4) Cohort K+1: BV on Day 1: 1.8 mg/kg (cycle 1-3) and 1.8 mg/kg (cycle 4) Cohort K-1: BV on Day 1: 0.8 mg/kg (cycle 1-3) and 1.8 mg/kg (cycle 4) Phase II: BV on Day 1: at the Maximal Tolerated Dose (MTD) defined at Phase I

Also known as: BV, SGN35

BV-ICE

Etoposide DRUG

100 mg/m² Days 1-2-3 of Cycles 1-2-3

BV-ICE

Carboplatine DRUG

max 800mg Day 2 of Cycles 1-2-3

BV-ICE

Ifosfamide DRUG

5 g/m² Day 2 of Cycles 1-2-3

BV-ICE

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed cluster of differentiation antigen 30 + (CD30+) HL, primarily refractory to first line chemotherapy or in first relapse after any polychemotherapy regimen
• Measurable disease defined as at least one single node or tumor lesion on CT scan \> 1.5 cm
• Fluorodeoxyglucose (FDG)-PET/ CT realized at relapse and positive.
• Age ≥ 18 years and up to 65 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 (see appendix 19.5)
• Life expectancy of \> 3 months with treatment
• No major organ dysfunction, unless HL-related
• Normal cardiac and pulmonary function for auto transplantation
• Total bilirubin \< 1.5 x ULN (unless due to lymphoma involvement of the liver or a known history of Gilbert's syndrome)
• Alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2 x ULN (unless due to lymphoma involvement of the liver : ≤ 5 x ULN)
• Creatinine clearance \> 60 mL/min
• Absolute neutrophil count ≥ 1.5x109/L, unless caused by diffuse bone marrow infiltration by the HL
• Platelets ≥ 100x109/L, unless caused by diffuse bone marrow infiltration by the HL
• Hemoglobin must be ≥ 8g/dL
• Written informed consent

You may not qualify if:

• Peripheral sensory or motor neuropathy grade ≥ 2
• Any chemotherapy, radiotherapy, immunotherapy or investigational, therapy for treatment of lymphoma within 28 days prior Cycle1 Day1
• Patient who have been treated by first line of treatment with brentuximab vedotin alone or in combination
• Female patients who are both lactating and breast feeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test 4 days prior the start of study drug
• Patients with active, uncontrolled infections (requiring systemic antibiotics within two weeks prior to treatment)
• Prior history of another cancer unless the subject has been free of the disease for ≥ 3 years (with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 or carcinoma in situ of the uterine cervix)
• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive multifocal leukoencephalopathy
• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin.
• Known history of human immunodeficiency virus (HIV), or known active Hepatitis C Virus, or active Hepatitis B Virus (HBV) infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
• Patients with a psychiatric disorder that would preclude compliance with drug delivery
• Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study such as:
• unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 2 years prior to first study drug administration, serious uncontrolled cardiac arrhythmia, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• cerebrovascular accident ≤ 6 months before study drug start recent evidence (within 6 months before first dose of study drug)
• a left-ventricular ejection fraction \<50%
• severely impaired pulmonary function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) that is 50% or less of the normal predicted value and/or O2 saturation that is 90% or less at rest on room air

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (19)

Clinique Universitaire Saint-Luc

Brussels, 1200, Belgium

Location

CHU Dinant Godinne

Yvoir, 5530, Belgium

Location

Institut d'Hématologie de Basse Normandie - CHU Côte de Nacre

Caen, 14033, France

Location

APHP-Hôpital Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon - Hôpital le Bocage

Dijon, 21000, France

Location

CHRU Lille - Hôpital Claude Huriez

Lille, 59037, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

CHU Saint Eloi

Montpellier, 34295, France

Location

CHU De Nantes

Nantes, 44093, France

Location

Hôpital Necker

Paris, 75015, France

Location

APHP - Hôpital Saint Louis

Paris, 75475, France

Location

CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Poitiers - Hôpital de La Milétrie

Poitiers, 86021, France

Location

CHU De Rennes

Rennes, 35033, France

Location

Centre Henri Becquerel

Rouen, 76000, France

Location

CHU De Strasbourg

Strasbourg, 67098, France

Location

IUCT Toulouse

Toulouse, 31100, France

Location

CHU De Nancy - Hôpital Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, 94085, France

Location

Related Publications (1)

• Stamatoullas A, Ghesquieres H, Feugier P, Andre M, Le Bras F, Gac AC, Borel C, Gastinne T, Quittet P, Morschhauser F, Ribrag V, Guidez S, Nicolas-Virelizier E, Berriolo-Riedinger A, Vander Borght T, Edeline V, Brice P. Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study. Leuk Lymphoma. 2022 Dec;63(13):3063-3071. doi: 10.1080/10428194.2022.2107204. Epub 2022 Aug 17.

  PMID: 35975738 DERIVED

MeSH Terms

Conditions

Hodgkin Disease; Recurrence

Interventions

Brentuximab Vedotin; Etoposide; Carboplatin; Ifosfamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pauline Brice, MD

  Lymphoma Study Association

  PRINCIPAL INVESTIGATOR

• Aspasia Stamatoullas Bastard, MD

  Lymphoma Study Association

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: February 19, 2016
• Study Start: March 1, 2016
• Primary Completion: October 31, 2018
• Study Completion: July 12, 2021
• Last Updated: December 7, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); FR (17)