PHASE I-II CLINICAL TRIAL FOR THE EVALUATION OF THE ROLE OF BRENTUXIMAB VEDOTIN PLUS ETOPOSIDE, SOLUMODERIN, HIGH DOSE ARA-C AND CIS-PLATIN IN THE TRANSPLANT AND POST-TRANSPLANT MANAGEMENT FOR PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA
- Conditions
- CLASSICAL HODGKIN LYMPHOMAMedDRA version: 17.0 Level: HLGT Classification code 10025319 Term: Lymphomas Hodgkin's disease System Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2014-000835-17-ES
- Lead Sponsor
- GELTAMO (Grupo Cooperativo Español de Linfoma/Trasplante Autólogo de Médula Ósea)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 66
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
Each patient must meet all of the following inclusion criteria to be enrolled in this study:
1. Patients with histologically confirmed relapsed or refractory classical HL after first line chemotherapy. CD30 has to be positive in tumor cells based on any previous lymph node immunohistochemistry. Lymphocyte predominance (LP) Hodgkins Lymphoma with LP CD30 [neg] cells will be excluded.
2. Age 18 to 65 years. Patient >65 years old with ECOG =1 and absence of comorbidities will be included in the study if considered adequate by the investigator.
3. ECOG = 2.
4. No major organ dysfunction.
5. Written informed consent.
6. Biopsy at HL relapse or when refractoriness disease is diagnosed must be done prior to BV-ESHAP. If biopsy cannot be performed, tumor biopsy at initial diagnosis of HL must be available to be revised by reference pathologist if required.
7. Absence of prior history of other malignant diseases, except:
- Basal cell carcinoma of the skin or uterine in situ carcinoma adequately treated.
- Any curable neoplasia adequately treated that has achieved complete response and has remained in such status longer than 3 years.
8. Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree 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.
9. 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.
10. Karnofsky performance status =60.
11. Life-expectancy >3 months.
12. Baseline platelet count =75x109 /L (or 20 if due to Bone Marrow [BM] infiltration) absolute neutrophil count =1.5x109 /L (or 0.5 if due to BM infiltration), andhemoglobin must be = 8g/dL.
13. Meet the following pretreatment laboratory criteria at the Screening visit conducted within 28 days of study enrollment:
- Total Bilirubin: <1.5 times the upper limit of institutional laboratory normal, unless clearly related to the disease (Gilbert disease will be ruled out from this point).
- AST (SGOT):<3times the upper limit of institutional laboratory normal except liver infiltration.
- ALT (SGPT):<3 times the upper limit of institutional laboratory normalexcept liver infiltration.
- Serum creatinine must be < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute
- Serum sodium >130 mmol/L
14. Voluntary written informed consent 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.
Are the trial s
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
2. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
3. Patients that have been treated previously with anti-CD30 monoclonal antibodies cannot be enrolled in the study.
4. Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, congestive heart failure (NYHA III-IV), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any EKG abnormality
at Screening has to be documented by the investigator as not medically relevant.Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%.
5. Peripheral neuropathy or neuropathic pain grade 2 or higher as defined by NCI CTCAE version 4
6. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML
7. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
8. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximabvedotin.
9. Women who are pregnant. Women who are breast-feeding and do not consent to discontinue breast-feeding. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence. Women of childbearing potential must have a negative pregnancy test at screening and cycle 1 day 1 prior to the first dose of brentuximabvedotin.
10. Treatment with any known non-marketed drug substance or experimental therapy within the longer of 5 terminal half-lives or 4 weeks prior to enrollmentor currently participating in any other interventional clinical study
11. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment within two weeks prior to first study drug dose such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
12. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
13. Known HIV positive
14. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.
15. Positive serology for hepatitis B (HBV) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method