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

NCT02280993 | Unknown Phase 1 DMC

• 3 other identifiers: Transplant BRaVENL40688.018.122012-003097-45
• Study Type: interventional
• Target: 72
• Locations: 4 countries
• Sites: 13

Brief 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 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).

Conditions

Hodgkin Lymphoma; Refractory; Relapse

Outcome Measures

Primary Outcomes (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)

  12 weeks

Secondary Outcomes (1)

• (Severe) Adverse Event

  12 weeks

Other Outcomes (1)

• Response

  12 weeks

Study Arms (1)

DHAP-BV

EXPERIMENTAL

Brentuximab Vedotin with DHAP chemotherapy follow by Autologous Peripheral Blood Stem Cell Transplantation

Drug: DHAP; Drug: Brentuximab Vedotin; Other: Autologous Peripheral Blood Stem Cell Transplantation

Interventions

DHAP DRUG

DHAP

Also known as: Dexamethasone, AraC, Cisplatin

DHAP-BV

Brentuximab Vedotin DRUG

Brentuximab Vedotin

Also known as: Adcetris, SGN-35

DHAP-BV

Autologous Peripheral Blood Stem Cell Transplantation OTHER

Autologous Peripheral Blood Stem Cell Transplantation

Also known as: ASCT

DHAP-BV

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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.
• Patients with any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
• 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

Sponsors & Collaborators

• Marjolein Spiering: lead
• Millennium: The Takeda Oncology Company: collaborator

Study Sites (13)

Rigshospitalet

Copenhagen, Denmark

Location

Centre Hospitalier Universitaire

Lille, France

Location

Hospices Civils de Lyon

Lyon, France

Location

Centre Hospitalier et Universitaire

Nantes, France

Location

Hôpital Saint Louis

Paris, France

Location

Institut Gustave Roussy

Paris, France

Location

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

Free University Medical Center

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Cambridge University Hospitals NHS Foundation Trust | Addenbrooke's Hospital

Cambridge, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, United Kingdom

Location

Christie Hospital, Manchester

Manchester, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 37722357 DERIVED

• 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.

  PMID: 36241696 DERIVED

• 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.

  PMID: 32273476 DERIVED

Related Links

• Transplant BRaVE

MeSH Terms

Conditions

Hodgkin Disease; Recurrence

Interventions

Dexamethasone; Cisplatin; Brentuximab Vedotin

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Anton Hagenbeek, PhD MD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• Marie José Kersten, PhD MD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• Marjolein Spiering, MSc

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: November 3, 2014
• Study Start: May 1, 2014
• Primary Completion: November 1, 2018
• Study Completion: May 1, 2020
• Last Updated: March 13, 2018

Record last verified: 2018-03

Locations

GB (3); DK (1); FR (5); NL (4)