Study of the efficiency of brentuximab vedotin in the Hodgkin lymphoma treatment for the patients not cured by standard chemotherapy.

Phase 1

Conditions: Patients aged from 18 to 70 years with supradiaphragmatic Ann Arbor clinical stage I or II classical Hodgkin lymphoma CD30+, FDG-PET positive score 4 & 5 according to Deauville criteria after 2 courses of ABVD will be included in the trial.
MedDRA version: 20.0Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-000734-35-BE

Lead Sponsor: YSARC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

1. Patients must have histologically confirmed CD30+ classical Hodgkin lymphoma
2. Patients must have provided voluntary written informed consent before performance of any study-related procedures not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
3. Supradiaphragmatic Ann Arbor clinical stage I or II (favourable and unfavourable according to the EORTC/GELA clinical prognostic factors)
4. Mandatory FDG-PET/ CT without IV contrast performed at diagnosis
5. Patients treated with first-line ABVD and FDG-PET positive after 2 cycles (Deauville score 4&5) and without progressive disease
6. Patients must have an ECOG performance status of 0-2
7. Life expectancy > 6 months
8. Patients must be 18-70 years of age
9. Patients must be available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution
10. Clinical laboratory values as specified below before the first dose of study drug:
• Absolute neutrophil count = 1,500/µL
• Platelet count = 75,000/ µL Total bilirubin must be < 1.5 x the upper limit of the normal (ULN) unless the elevation is known to be due to Gilbert syndrome
• ALT or AST must be < 3 x the upper limit of the normal range
• Serum creatinine must be < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute
• Hemoglobin must be = 8g/dL
11. Patient affiliated to social security system

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Patients with dementia or altered mental status that would preclude compliance with drug delivery
2. Women who are pregnant or breastfeeding
3. Patients with symptomatic pulmonary disease
4. Patients with known history of any of the following cardiovascular conditions:
• Myocardial infarction within 2 years of inclusion
• New York Heart Association (NYHA) Class III or IV heart failure
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or 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%
5. Any history of cancer or cancer treatment during the last 3 years with the exception of non-melanoma skin cancer or stage 0 (in situ) carcinoma of any type if they have undergone complete resection
6. Uncontrolled infectious disease, including active HBV infection defined by either detection of HBs Antigen or presence of anti HBc antibody without detectable anti HBs antibody
7. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics at the time of inclusion and planned to be still on going within 2 weeks prior to first study drug dose
8. Known HIV, known or suspected HCV serology positivity
9. Patients who have been treated previously with any anti-CD30 antibody
10. Known hypersensitivity to any excipients contained in the brentuximab vedotin formulation
11. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencephalopathy (PML)
12. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2
13. Patients that have not completed any prior treatment chemotherapy, except ABVD, and/or other investigational agents within at least 5 half-lives of last dose of that prior treatment

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluation of PFS at 2 years of the Brentuximab vedotin as consolidation treatment in patients with stage I/II Hodgkin’s lymphoma and FDG-PET positivity after 2 cycles of ABVD.;Secondary Objective: - Safety and evaluation of toxicities (hematological, neurological, cardiac and pulmonary) of brentuximab vedotin given after radiotherapy<br>- CR rate (Cheson 2007) at the end of treatment<br>- Overall Survival<br>;Primary end point(s): The primary efficacy endpoint is progression-free survival (PFS) according to investigator assessment. <br>;Timepoint(s) of evaluation of this end point: Evaluation of the PFS at two years.<br>PFS is defined as the time from the date of the first cycle of ABVD to the first observation of documented disease progression or death due to any cause. If a subject has not progressed or died, PFS will be censored at the time of last visit with adequate assessment. <br><br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • To evaluate the safety and tolerability of brentuximab vedotin<br>• To analyze overall survival (OS) and CR rate (Cheson 2007) at the end of treatment<br><br>;Timepoint(s) of evaluation of this end point: • RESPONSE RATE ACCORDING TO THE RESPONSE CRITERIA FOR MALIGNANT LYMPHOMA 2007<br>Response rate (Complete Response) will be evaluated after 8 cycles of brentuximab vedotin. Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin’s lymphoma (Cheson, 2007). Patient without response assessment (due to whatever reason) will be considered as non-responder.<br>• OVERALL SURVIVAL (OS)<br>Overall survival will be measured from the date of the first cycle of ABVD to the date of death from any cause. Alive patients will be censored at their last follow-up date. <br>

Related Trials