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Hodgkin DiseasePhase 1/2BV-ICENCT02686346

Brentuximab Vedotin in Refractory/Relapsed Hodgkin Lymphoma Treated by ICE

A Phase 1/2 study testing Brentuximab Vedotin, Etoposide and Carboplatine in people with Hodgkin Disease, run by The Lymphoma Academic Research Organisation at 19 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Hodgkin Disease
What is being tested?
Brentuximab Vedotin, Etoposide and Carboplatine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
19 sitesin 2 countries
Study dates
Mar 2016to 12 Jul 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Able to adhere to the study visit schedule and other protocol requirements
  • Eligible for high dose chemotherapy and autologous peripheral blood stem cell transplantation
  • Resolution of toxicities from first-line therapy
  • Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
  • Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.

Who cannot join

  • 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)
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  • 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
  • any active (acute or chronic) or uncontrolled disorders that impair the ability to evaluate the patient or for the patient to complete the study
  • any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
  • nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study drug, such as severe hypertension that is not controlled with medical management and thyroid abnormalities when thyroid function cannot be maintained in the normal range

Trial locations and contacts

19 sites in 2 countries.

19 sites in 2 countries

France17 sites

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

    Caen, 14033

  • APHP-Hôpital Henri Mondor

    Créteil, 94010

  • CHU de Dijon - Hôpital le Bocage

    Dijon, 21000

  • CHRU Lille - Hôpital Claude Huriez

    Lille, 59037

  • Centre Léon Bérard

    Lyon, 69373

  • CHU Saint Eloi

    Montpellier, 34295

  • CHU De Nantes

    Nantes, 44093

  • Hôpital Necker

    Paris, 75015

  • APHP - Hôpital Saint Louis

    Paris, 75475

  • CHU Lyon Sud

    Pierre-Bénite, 69495

  • CHU de Poitiers - Hôpital de La Milétrie

    Poitiers, 86021

  • CHU De Rennes

    Rennes, 35033

  • Centre Henri Becquerel

    Rouen, 76000

  • CHU De Strasbourg

    Strasbourg, 67098

  • IUCT Toulouse

    Toulouse, 31100

  • CHU De Nancy - Hôpital Brabois

    Vandœuvre-lès-Nancy, 54511

  • Institut Gustave Roussy

    Villejuif, 94085

Other trials in France

Belgium2 sites

  • Clinique Universitaire Saint-Luc

    Brussels, 1200

  • CHU Dinant Godinne

    Yvoir, 5530

Other trials in Belgium

About this study

Official title: Phase I/II Feasibility Study of Brentuximab Vedotin in Refractory / Relapsed Hodgkin Lymphoma Patients Who Are Treated by Chemotherapy (ICE) in Second Line and Eligible for Autologous Transplantation

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.

Read the detailed description

PHASE I:

3 cycles of Brentuximab Vedotin ICE every 3 weeks and one cycle of Brentuximab Vedotin alone at the doses described below.

Cohorts of between three and six evaluable patients will be recruited at each dose level.

Dose escalation rules:

Treat 3 patients at level K

  1. If 0 patients experience dose-limiting toxicity (DLT), escalate to dose K+1
  2. If 2 or more patients experience DLT, de-escalate to level K-1
  3. If 1 patient experiences DLT, treat 3 more patients at dose level K A. If 1 of 6 experiences DLT, escalate to dose level K+1 B. If 2 or more of 6 experiences DLT, de-escalate to level K-1 Dose escalation will begin at level K.

Level K:

Brentuximab Vedotin: 1.2 mg/kg (cycle 1-3), 1.8 mg/kg (cycle 4) ICE (cycle 1-3): Etoposide 100 mg/m² (day1 to 3); Carboplatine max 800mg (day 2); Ifosfamide + Mesna 5 g/m² (day 2)

Level K -1:

Brentuximab Vedotin: 0.8 mg/kg (cycle 1-3), 1.8 mg/kg (cycle 4) ICE (cycle 1-3): Etoposide 100 mg/m² (day1 to 3); Carboplatine max 800mg (day 2); Ifosfamide + Mesna 5 g/m² (day 2)

Level K +1:

Brentuximab Vedotin: 1.8 mg/kg (cycle 1-3), 1.8 mg/kg (cycle 4) ICE (cycle 1-3): Etoposide 100 mg/m² (day1 to 3); Carboplatine max 800mg (day 2); Ifosfamide + Mesna 5 g/m² (day 2)

Dose finding rule:

Provisional dose levels are listed in previous tables. Dose-escalation will continue until Maximal Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is reached or the full doses of BV and ICE are delivered without DLT

PHASE II:

3 cycles of Brentuximab Vedotin + ICE every 3 weeks and one cycle Brentuximab Vedotin alone.

The recommended dose of BV and ICE will be determined by the phase I Brentuximab Vedotin: MTD mg/kg (cycle 1-3), 1.8 mg/kg (cycle 4) ICE (cycle 1-3): Etoposide 100 mg/m² (day1 to 3); Carboplatine max 800mg (day 2); Ifosfamide + Mesna 5 g/m² (day 2) The recommended dose of BV and ICE will be determined by the phase I.

Conditions
Hodgkin Disease
Being tested
Brentuximab Vedotin, Etoposide, Carboplatine, Ifosfamide
Keywords
Relapsed, Refractory
Medical subject headings
Hodgkin Disease, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brentuximab VedotinDrug

    Also called BV, SGN35

    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

  • EtoposideDrug

    100 mg/m² Days 1-2-3 of Cycles 1-2-3

  • CarboplatineDrug

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

  • IfosfamideDrug

    5 g/m² Day 2 of Cycles 1-2-3

Study groups in NCT02686346
Study groupRoleWhat they receive
BV-ICEExperimentalPhase 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
Receives: Drug: Brentuximab Vedotin; Drug: Etoposide; Drug: Carboplatine; Drug: Ifosfamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 4 months

  2. 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

    Measured: 2 months

Secondary outcomes (10)

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

    To characterize the safety and tolerability of BV in patient treated with ICE.

    Measured: 4 months

  2. Phase I = Preliminary Overall Response Rate (ORR)

    To assess preliminary anti-tumor activity of BV in patient treated with ICE.

    Measured: 4 months

  3. Phase II = ORR

    To assess the ORR (Complete Response and Partial Response) after 3 cycles of BV and ICE and one cycle of BV

    Measured: 4 months

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

    To assess the toxicity profile of BV in patient treated with ICE

    Measured: 4 months

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

    To assess hematological recovery after each cycle of BV and ICE

    Measured: 4 months

  6. Phase II = Feasibility of Autologous Stem Cell Transplant (ASCT) after BV-ICE = fraction of patients for whom harvest is possible

    To assess the feasibility of harvesting an autologous peripheral blood stem cell graft after BV in patient treated with ICE

    Measured: 4 months

  7. Phase II = Fraction of patients eligible for ASCT

    To assess the fraction of patients (Complete Response/Partial Response) eligible for ASCT who actually underwent one or two ASCT

    Measured: 4 months

  8. Phase II = Number of patients Positron Emission Tomography (PET) 4- after PET 2+

    To assess the number of patients with PET 4 negative if the PET 2 is positive

    Measured: 4 months

  9. Phase II = Progression Free Survival (PFS)

    Number of participants who did not progressed after 2 years

    Measured: 2 years

  10. Phase II = Overall Survival (OS)

    Number of participants alive after 2 years

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2016 (estimated)
  2. Study startMar 2016
  3. Primary completion31 Oct 2018
  4. Study completion12 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02686346
Sponsor's protocol ID
BV-ICE
Acronym
BV-ICE
Status last verified
Dec 2021
First submitted
9 Feb 2016
Last updated
7 Dec 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 35975738

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Brentuximab Vedotin, Etoposide and Carboplatine in people with Hodgkin Disease, run by The Lymphoma Academic Research Organisation at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I : Maximal Tolerated Dose (MTD) determination (time frame: 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02686346, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2021.

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