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BrEPEM-LH-22017 for Older Patients With Untreated Hodgkin Lymphoma (HL)

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ClinicalTrials.gov Identifier: NCT03576378
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : May 6, 2019
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Brief Summary:
The purpose of the phase Ib of the study is to identify the maximum tolerated dose (MTD) of Brentuximab Vedotin (BV) in combination with EPEM and to assess the toxicity of the combination of BV with EPEM. In the phase II efficacy will be evaluated.Besides, progression-free survival (PFS), event-free survival (EFS), overall survival (OS), the duration of response, the overall response rate (ORR) based on best response will be evaluated

Condition or disease Intervention/treatment Phase
Hodgkin Lymphoma Drug: BrentuximabVedotin (BV) Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Trial of Combined SGN-35 (BrentuximabVedotin) Therapy With Cyclophosphamide, Procarbazine, Prednisone, Etoposide and Mitoxantrone (BrEPEM) for Older Patients With Untreated Hodgkin Lymphoma (HL)
Actual Study Start Date : August 8, 2018
Estimated Primary Completion Date : October 30, 2023
Estimated Study Completion Date : October 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental: Brentuximab vedotin plus EPEM
Brentuximab Vedotin dose will start at 1.2 mg/kg by intravenous (IV) infusion on Day1 and Day15 plus Cyclophosphamide 500mg/m2 IV on Day1 plus Procarbazine 100mg/m2 by mouth (OR) on Day1 through 5 plus Etoposide 60mg/m2 OR on Day15 through 19 plus Mitoxantrone 6mg/m2 IV on Day15 and Prednisone 30mg/m2 on Day1 through 5 of each 28-day treatment cycles for up to 6 total treatment cycles (approximately 24 weeks or 6 months)
Drug: BrentuximabVedotin (BV)
All patients will be treated with 6 cycles of BV-EPEM
Other Names:
  • cyclophosphamide
  • procarbazine
  • prednisone
  • etoposide
  • mitoxantrone




Primary Outcome Measures :
  1. Phase Ib: maximum tolerated dose (MTD) [ Time Frame: Up to 28 days after start of each cycle ]
    To identify the maximum tolerated dose (MTD) of Brentuximab Vedotin (BV) in combination with EPEM

  2. Phase II: Complete response rate [ Time Frame: 6 months after last patient start treatment ]
    To assess the percentage of patients with complete response rate after BV-EPEM treatment.

  3. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 28 days after start of each cycle ]
    To evaluate the toxicity of the treatment by measure of number of treatment-related adverse events according to CTCAE v4.0


Secondary Outcome Measures :
  1. progression-free survival (PFS) [ Time Frame: At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study ]
    Evaluation of patient without progression of disease

  2. Duration of response [ Time Frame: At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study ]
    length of time between date of evidence response and progression of disease or death

  3. Overall response rate (ORR) [ Time Frame: At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study ]
    To evaluate overall response rate (ORR) based on best response (CR and PR) and the tumor local control rate (CR, PR, and stable disease [SD]) with this treatment regimen.

  4. Incidence of Treatment Adverse Events [Safety and Tolerability] [ Time Frame: At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study ]
    To assess the type, frequency, severity and relationship of adverse events (AEs) to this treatment regimen.

  5. event-free survival (EFS) [ Time Frame: At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study ]
    evaluation of patients without events

  6. overall survival (OS) [ Time Frame: At the end of eache cycle (every cycle is 28 days) and then every 3 months up to 3 years in the study ]
    evaluation of patients alive after first dose of treatment and follow up



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Ages Eligible for Study:   60 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females of 60 years of age or older.
  2. Previously untreated classical Hodgkin lymphoma (i.e., nodular sclerosis, mixed cellularity, lymphocyte depleted, lymphocyte-rich, and not otherwise specified [NOS]).
  3. Stage IIB, III, and IV disease by Ann Arbor classification.
  4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
  5. Patients must have bi-dimensional measurable disease documented in the lymphoma baseline tumor assessment form (PET-CT report) within 30 days prior to Screening (at least 1.5 cm)
  6. Patients must have a bone marrow biopsy within 60 days prior to screening.
  7. Patients must have a multi gated acquisition scan (MUGA) or echocardiogram within 60 days prior to study screening and the ejection fraction must be >= 50%.
  8. Adequate hematologic function, defined as Absolute neutrophil count (ANC) ≥ 1,500/mm3 / 1x109/L and Platelet count ≥75,000/mm3 / 75x109/L unless there is known marrow involvement of the disease
  9. Serum Creatinine < 2.0 mg/dl and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute.
  10. Total Bilirubin < 1.5 x the upper limit of normal (ULN) unless elevation is known to be due to Gilbert syndrome.
  11. ALT or AST must be < 3 x the upper limit of the normal range. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of hematologic/solid tumour in liver.
  12. Hemoglobin must be ≥ 8g/dL
  13. Patients must not have received prior chemotherapy or radiation therapy for the treatment of Hodgkin lymphoma.
  14. Female patient is either post-menopausal for at least 2 years before the screening visit or surgically sterile or if of childbearing potential must agree to use two effective contraceptive methods, at the same time, from the time of signing the informed consent and for 6 months following the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
  15. Male patients, even if surgically sterilized, (i.e., status post vasectomy) must agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
  16. Patients must sign the informed consent form before screening. Voluntary written informed consent must be signed before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

  1. Nodular lymphocyte predominant Hodgkin lymphoma
  2. Previous treatment with BV or any other prior anti-CD30-based antibody therapy
  3. Female patient who is both lactating and breast-feeding or has a positive pregnancy test during the screening period or a positive pregnancy test on Day 1 before the first dose of study drug
  4. History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: early stage [stage I or II] breast cancer treated with surgery and radiation +/- hormones [without adjuvant chemotherapy], non-melanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou test [PAP smear])
  5. Known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML)
  6. Any active systemic viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 1 week prior to first dose
  7. Known or suspected hepatitis B infection, or known or suspected active hepatitis C infection Known human immunodeficiency virus (HIV) positive
  8. Patients with a known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin
  9. Patients with dementia or an altered mental state that would preclude the understanding and rendering of informed consent
  10. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
  11. Any sensory or motor peripheral neuropathy greater than or equal to 2
  12. Known history of any of the following cardiovascular conditions;

    1. Myocardial infarction within 2 years of enrollment
    2. New York Heart Association (NYHA) Class III or IV heart failure
    3. Evidence of uncontrolled cardiovascular conditions, including cardiac arrhythmias,congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03576378


Contacts
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Contact: FRANCESC BOSCH, MD, PhD +0034 913913383 fbosch@vhio.net
Contact: LUCIA PALACIOS, BsC +0034 913913383 ensayosclinicos01@geltamo.com

Locations
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Spain
Institut Català d'Oncologia, Hospital Germans Trias i Pujol Recruiting
Badalona, Barcelona, Spain
Contact: Miriam Moreno Velázquez, MD       miriammv10@hotmail.com   
Principal Investigator: Miriam Moreno Velázquez, MD         
Institut Català d'Oncologia, Hospital Duran i Reynals Recruiting
L'Hospitalet De Llobregat, Barcelona, Spain
Contact: Eva Domingo, MD       edomingo@iconcologia.net   
Principal Investigator: EVA Domingo, MD         
Hospital Costa del Sol Recruiting
Marbella, Málaga, Spain
Contact: Maria Casanova, MD       mariacasanova@yahoo.com   
Principal Investigator: Maria Casanova, MD         
Hospital Clinic i Provincial de Barcelona Recruiting
Barcelona, Spain
Contact: Carmen Martínez, MD       cmarti@clinic.ub.es   
Principal Investigator: Carmen Martínez, MD         
Hospital Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Cecilia Carpio, MD       cecicar2@gmail.com   
Principal Investigator: Cecilia Carpio, MD         
Hospital de Basurto Recruiting
Bilbao, Spain
Contact: Cristina Barrenetxea, MD       cristina.barrene@gmail.com   
Principal Investigator: Cristina Barrenetxea, MD         
Hospital General Universitario Gregorio Marañon Recruiting
Madrid, Spain
Contact: Mariana Bastos, MD       bastosmariana@yahoo.com   
Principal Investigator: Mariana Mastos, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: Antonia Rodriguez, MD       antonia.rodriguez@salud.madrid.org   
Principal Investigator: Antonia Rodriguez, MD         
Hospital Universitario La Paz Recruiting
Madrid, Spain
Contact: Pilar Gomez Prieto, MD       pilargp84@gmail.com   
Principal Investigator: Pilar Gomez Prieto, MD         
Hospital Son Llatzer Recruiting
Palma De Mallorca, Spain
Contact: Antonia Cladera Serra, MD       acladera@hsll.es   
Principal Investigator: Antonia Cladera Serra, MD         
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain
Contact: Ramón García-Sanz, MD       rgarcias@usal.es   
Principal Investigator: Ramón García-Sanz, MD         
Hospital Universitario Donostia - Arantzazu Recruiting
San Sebastián, Spain
Contact: Izaskun Ceberio, MD       izaskun.ceberioechechipia@osakidetza.eus   
Principal Investigator: Izaskun Ceberio, MD         
Hospital Universitario Marqués de Valdecilla Recruiting
Santander, Spain
Contact: Javier Nuñez Cespedes, MD       javier.nunecespedes@gmail.com   
Principal Investigator: Javier Nuñez Cespedes, MD         
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain
Contact: Fátima De la Cruz Vicente, MD       fatimadelacruzv@gmail.com   
Principal Investigator: Fátima De la Cruz Vicente, MD         
Hospital Universitario Miguel Servet Recruiting
Zaragoza, Spain
Contact: Araceli Rubio Martinez, MD       arubiom@salud.aragon.es   
Principal Investigator: Araceli Rubio Martinez, MD         
Sponsors and Collaborators
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Takeda

Publications:

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Responsible Party: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
ClinicalTrials.gov Identifier: NCT03576378     History of Changes
Other Study ID Numbers: BrEPEM-LH-22017
First Posted: July 3, 2018    Key Record Dates
Last Update Posted: May 6, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Prednisone
Etoposide
Etoposide phosphate
Mitoxantrone
Procarbazine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors