Brentuximab vedotin associated with chemotherapy in untreated patients with stage I/II unfavourable Hodgkin lymphoma

Phase 1

Conditions: Hodgkin Lymphoma
MedDRA version: 17.1Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-000182-37-IT

Lead Sponsor: YSARC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 170

Inclusion Criteria

- Histologically confirmed CD30+ classical Hodgkin lymphoma according to local evaluation
- Supradiaphragmatic Ann Arbor clinical stage I or II
- Previously untreated
- PET scan without IV contrast at diagnosis available for central review with at least one hypermetabolic lesion
- Unfavourable (U) characteristics according to the classic EORTC/LYSA clinical prognostic factors. Unfavourable (U) subset includes patients with at least one of the following factors:
a) CSII = 4 nodal areas
b) age = 50 yrs
c) M/T ratio = 0.35
d) ESR = 50 (without B-symptoms) or ESR = 30 with B-symptoms
- ECOG performance status 0-2
- Life expectancy > 6 months
- Age 18 to 60 years (= 18 years to = 60 years)
- Patients must be available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution.
- Female patients who:
a) Are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile,
OR
b) If they are 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 agree to
completely abstain from heterosexual intercourse
- Male patients, even if surgically sterilized (ie, status postvasectomy), who:
a) Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
- Patients must give written informed consent. A copy of the informed signed consent form will be retained in the patient’s chart.
- Required baseline laboratory data:
a) Absolute neutrophil count = 1,500/µL
b) Platelet count = 75,000/ µL
c) Hemoglobin = 8g/dL
d) Serum total bilirubin = 1.5 X ULN unless the elevation is known to be due to Gilbert syndrome.
e) Serum creatinine = 2.0 mg/dL and/or calculated creatinine clearance > 40 mL/minute (Cockcroft-Gault formula or MDRD)
f) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 X ULN

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 170
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Histological diagnosis different from classical Hodgkin Lymphoma. Nodular lymphocyte predominant subtypes (nodular paragranuloma or Poppema paragranuloma) are excluded
- Known cerebral or meningeal disease of any etiology, including signs or symptoms of PML
- Any sensory or motor peripheral neuropathy = Grade 2
- Known history of any of the following cardiovascular conditions
a) Myocardial infarction within 2 years of randomization
b) New York Heart Association (NYHA) Class III or IV heart failure
c) 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
d) Recent evidence (within 30 days before first dose of study drug) of a leftventricular ejection
fraction <50%
- Unstable diabetes mellitus (to avoid uninterpretable FDG-PET scan).
- Known HIV positive
- HCV positive
- HBV positive. This means:
a) HBsAg positive
b) HBsAg negative, anti-HBs positive and/or anti-HBc positive and
detectable viral DNA
c) Note:
* Patients who are HBsAg negative and viral DNA negative are eligible
* Patients who are seropositive due to a history of hepatitis B vaccine are eligible.
- Any history of cancer during the last 5 years, with the exception of nonmelanoma skin tumors. Carcinoma
in situ of any type are not excluded if they have undergone complete resection.
- Dementia or altered mental status that would preclude compliance with drug delivery
- Pregnancy or breastfeeding. Females of childbearing potential having a positive ß-HCG pregnancy test result during screening or a positive pregnancy test (urinary or blood) within 1 day before start of treatment.
- Previous treatment with any anti-CD30 antibody
- Known hypersensitivity to any excipients contained in the brentuximabvedotin formulation or known contra-indication to any drug contained in thechemotherapy regimens (for ex.: pulmonary or neurological disease grade =2)
- Treatment with corticosteroids before baseline PET scan (PET-0)
- Patients with known active viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy or with untreated known active Grade 3 viral, bacterial, or fungal infection, within 2 weeks prior to the first dose of brentuximab vedotin
- Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy or immuno-chemotherapy

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To improve the PET negativity after two cycles of immuno-chemotherapy<br>;Secondary Objective: Secondary efficacy endpoint:<br>- CR rate (according to Cheson 2007) at the end of treatment <br>- Progression-free survival (PFS)<br>- Overall survival <br><br>Secondary safety endpoint: <br>- Toxicity of brentuximab vedotin in combination with combined modality treatment ;Primary end point(s): PET 2 assessment according to the five-point scale Deauville criteria (Negative = 1, 2, 3 and Positive = 4, 5), based on central review.<br>;Timepoint(s) of evaluation of this end point: After 2 cycles of chemotherapy or immuno-chemotherapy (ABVD or AVD/Brentuximab vedotin)- 2 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary efficacy endpoint:<br>- CR rate (according to Cheson 2007) at the end of treatment <br>- Progression-free survival (PFS)<br>- Overall survival <br><br>Secondary safety endpoint: <br>- Toxicity of brentuximab vedotin in combination with combined modality<br>treatment ;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoint:<br>- Disease response evaluation at end of treatment (after radiotherapy) will be used to determine the Response Rate.<br>- PFS is defined as the time from randomization into the study 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 assessment.<br>- Overall survival will be measured from date of randomization into the study to the date of death from any cause. <br><br>Secondary safety endpoint: <br>- End of treatment

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