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Hodgkin LymphomaPhase 1NCT02280993

Phase I/II Feasibility Study Combining Brentuximab Vedotin With Second Line Salvage Chemotherapy (DHAP) in Hodgkin Lymphoma Patients

A Phase 1 study testing DHAP, Brentuximab Vedotin and Autologous Peripheral Blood Stem Cell Transplantation in people with Hodgkin Lymphoma and Refractory, run by Marjolein Spiering at 13 sites in 4 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To combine Brentuximab Vedotin with Dexamethasone, AraC and Cisplatin (DHAP) chemotherapy in patients with Hodgkin lymphoma (HL) refractory to first line chemotherapy or in first relapse is expected to induce a significantly higher (metabolic) complete remission (CR) rate prior to consolidation with BEAM, as judged by… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hodgkin Lymphoma, Refractory, Relapse
What is being tested?
DHAP, Brentuximab Vedotin and Autologous Peripheral Blood Stem Cell Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
13 sitesin 4 countries
Study dates
May 2014to May 2020
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed CD30+ classical HL (central pathology review; results not required to enroll the patient in the study), primarily refractory to first line chemotherapy or in first relapse after any polychemotherapy regimen (e.g. ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine), baseline BEACOPP ( bleomycin, etoposide, Adriamycin, cyclophosphamide, Oncovin, procarbazine, and prednisone) or escalated BEACOPP, or other induction regimens)
  • In case of relapse, the relapse must be histologically confirmed. In case histology is not possible, at least confirmation of the relapse by fine-needle aspiration is required.
  • Measurable disease, as defined in Appendix C i.e. CT scans showing at least 2 or more clearly demarcated lesions with a long axis ≥ 1.5 cm and a short axis diameter ≥ 1.0 cm, or 1 clearly demarcated lesion with a long axis ≥ 2.0 cm and a short axis diameter ≥ 1.0 cm. These lesions must be FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose)-positive
  • Age ≥ 18 years (upper age limit for auto stem cell transplantation at the discretion of the participating center)
  • WHO ≤ 2 (see appendix A)
  • Life expectancy of > 3 months with treatment
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  • No major organ dysfunction, unless HL-related
  • Total bilirubin < 1.5x ULN (unless due to lymphoma involvement of the liver or a known history of Gilbert's syndrome)
  • ALT/AST < 3x ULN (unless due to lymphoma involvement of the liver; in that case ALT/AST may be elevated up to 5 x ULN)
  • glomerular filtration rate (GFR) > 60 ml/min as estimated by the Cockcroft\&Gault formula (appendix D)
  • 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 >8 g/dL
  • Written informed consent
  • Able to adhere to the study visit schedule and other protocol requirements
  • Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days 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.
  • Eligible for high dose chemotherapy and autologous peripheral blood stem cell transplantation
  • Resolution of toxicities from first-line therapy

Who cannot join

  • Peripheral sensory or motor neuropathy grade ≥ 2
  • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy
  • Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
  • Patients who have been using other investigational agents within at least 5 half lives of the most recent agent used prior to enrollment in the study
  • Patients who were treated with myelosuppressive chemotherapy or biological therapy ≤ 4 weeks before study inclusion
  • 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 on Day 1 before first dose of study drug or adults of reproductive potential who are not using effective birth control methods.
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  • Patients with any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
  • Patients who have a history of another primary malignancy less than 3 years before study inclusion or previously diagnosed with another malignancy and have evidence of residual disease, with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 and carcinoma in situ of the uterine cervix
  • Patients with known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin.
  • Patients with known HIV seropositivity, known hepatitis B surface antigen-positivity, or known or suspected active hepatitis C infection
  • Patients receiving radiation therapy within 8 weeks prior to start of protocol treatment. Emergency radiation therapy is allowed, as long as measurable disease (at non-irradiated sites) persists.
  • Patients with a serious psychiatric disorder that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
  • Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study such as:Known history of symptomatic congestive heart failure (NYHA III, IV), myocardial infarction ≤ 6 months prior to first study drug
  • Evidence of current serious uncontrolled cardiac arrhythmia, angina pectoris, electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%
  • severely impaired pulmonary function as defined as spirometry and DLCO (diffusing capacity of the lung for carbon monoxide) 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 infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
  • 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 by medication

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

France5 sites

  • Centre Hospitalier Universitaire

    Lille

  • Hospices Civils de Lyon

    Lyon

  • Centre Hospitalier et Universitaire

    Nantes

  • Hôpital Saint Louis

    Paris

  • Institut Gustave Roussy

    Paris

Other trials in France

Netherlands4 sites

  • Academic Medical Center

    Amsterdam, 1105 AZ

  • Free University Medical Center

    Amsterdam

  • University Medical Center Groningen

    Groningen

  • Erasmus Medical Center

    Rotterdam

Other trials in Netherlands

United Kingdom3 sites

  • Cambridge University Hospitals NHS Foundation Trust | Addenbrooke's Hospital

    Cambridge

  • King's College Hospital NHS Foundation Trust

    London

  • Christie Hospital, Manchester

    Manchester

Other trials in United Kingdom

Denmark1 site

  • Rigshospitalet

    Copenhagen

Other trials in Denmark

About this study

Official title: Phase I/II Feasibility Study Combining Brentuximab Vedotin With Second Line Salvage Chemotherapy (DHAP) in Hodgkin Lymphoma Patients Refractory to First Line Chemotherapy or in First Relapse Who Are Eligible for High Dose Treatment Followed by Autologous Peripheral Blood Stem Cell Transplantation (ASCT)

To combine Brentuximab Vedotin with Dexamethasone, AraC and Cisplatin (DHAP) chemotherapy in patients with Hodgkin lymphoma (HL) refractory to first line chemotherapy or in first relapse is expected to induce a significantly higher (metabolic) complete remission (CR) rate prior to consolidation with BEAM, as judged by FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose)-PET negativity. This will be compared with published data on DHAP salvage only. Increasing the metabolic CR rate prior to consolidation with high dose chemotherapy and autologous stem cell transplantation (ASCT) is expected to improve progression free survival (PFS) and overall survival (OS).

Being tested
DHAP, Brentuximab Vedotin, Autologous Peripheral Blood Stem Cell Transplantation
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.

  • DHAPDrug

    Also called Dexamethasone, AraC, Cisplatin

    DHAP

  • Brentuximab VedotinDrug

    Also called Adcetris, SGN-35

    Brentuximab Vedotin

  • Autologous Peripheral Blood Stem Cell TransplantationOther

    Also called ASCT

    Autologous Peripheral Blood Stem Cell Transplantation

Study groups in NCT02280993
Study groupRoleWhat they receive
DHAP-BVExperimentalBrentuximab Vedotin with DHAP chemotherapy follow by Autologous Peripheral Blood Stem Cell Transplantation
Receives: Drug: DHAP; Drug: Brentuximab Vedotin; Other: Autologous Peripheral Blood Stem Cell Transplantation

What is being measured

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

  1. rate of patient with grade 4 Adverse Events

    The rate of patients with severe toxicity during cycle I-III of the combination treatment (BV + DHAP)

    Measured: 12 weeks

Secondary outcomes (1)

  1. (Severe) Adverse Event

    (Severe) Adverse Events during the combination treatment

    Measured: 12 weeks

Timeline

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

  1. First posted3 Nov 2014 (estimated)
  2. Study startMay 2014
  3. Primary completionNov 2018 (estimated)
  4. Study completionMay 2020 (estimated)

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
72 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02280993
Sponsor's protocol ID
Transplant BRaVE
Other IDs
NL40688.018.12, 2012-003097-45
Status last verified
Mar 2018
First submitted
19 Aug 2014
Last updated
13 Mar 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Driessen J, Zwezerijnen GJC, Schoder H, Kersten MJ, Moskowitz AJ, Moskowitz CH, Eertink JJ, Heymans MW, Boellaard R, Zijlstra JM. Prognostic model using 18F-FDG PET radiomics predicts progression-free survival in relapsed/refractory Hodgkin lymphoma. Blood Adv. 2023 Nov 14;7(21):6732-6743. doi: 10.1182/bloodadvances.2023010404.

    PubMed 37722357

  • Driessen J, Kersten MJ, Visser L, van den Berg A, Tonino SH, Zijlstra JM, Lugtenburg PJ, Morschhauser F, Hutchings M, Amorim S, Gastinne T, Nijland M, Zwezerijnen GJC, Boellaard R, de Vet HCW, Arens AIJ, Valkema R, Liu RDK, Drees EEE, de Jong D, Plattel WJ, Diepstra A; HOVON Lunenburg Lymphoma Phase I/II Consortium (LLPC). Prognostic value of TARC and quantitative PET parameters in relapsed or refractory Hodgkin lymphoma patients treated with brentuximab vedotin and DHAP. Leukemia. 2022 Dec;36(12):2853-2862. doi: 10.1038/s41375-022-01717-8. Epub 2022 Oct 14.

    PubMed 36241696

  • Kersten MJ, Driessen J, Zijlstra JM, Plattel WJ, Morschhauser F, Lugtenburg PJ, Brice P, Hutchings M, Gastinne T, Liu R, Burggraaff CN, Nijland M, Tonino SH, Arens AIJ, Valkema R, van Tinteren H, Lopez-Yurda M, Diepstra A, De Jong D, Hagenbeek A. Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study. Haematologica. 2021 Apr 1;106(4):1129-1137. doi: 10.3324/haematol.2019.243238.

    PubMed 32273476

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DHAP, Brentuximab Vedotin and Autologous Peripheral Blood Stem Cell Transplantation in people with Hodgkin Lymphoma and Refractory, run by Marjolein Spiering at 13 sites in 4 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 19 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: status not confirmed, as of the sponsor's last update on 13 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France, Netherlands, United Kingdom, Denmark. 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 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.

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

Are results available for this study?

Results are not available in the source record.

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?

rate of patient with grade 4 Adverse Events (time frame: 12 weeks). 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 NCT02280993, which also lists 3 linked publications.

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 13 Mar 2018.

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