E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma (ALCL) |
|
E.1.1.1 | Medical condition in easily understood language |
A type of cancer of lymph tissue |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10002235 |
E.1.2 | Term | Anaplastic large cell lymphomas T- and null-cell types |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the safety and tolerability of simultaneous administration of brentuximab vedotin and imatinib mesylate in substitution of conventional chemotherapeutic treatment. |
|
E.2.2 | Secondary objectives of the trial |
− Clinical response rate (ORR, CR, PR) − Ability to receive further treatment (stem cell transplantation) − Progression-free survival and overall survival − Identification and assessment of biomarkers Apart from clinical response rates with BV and imatinib, it seems important to evaluate, how many patients can go on to stem cell transplantation. sCD30 and PDGF can be determined in blood samples and should be evaluated as biomarkers. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients ≥ 18 years of age • ALK+ ALCL • Histologically confirmed relapse after having achieved a PR or CR with conventional therapy • Refractoriness to conventional chemotherapy (SD or PD after conventional chemotherapy) • Not able to receive conventional chemotherapy (e.g. due to comorbidities) • Adequate organ function, defined as the following: − Absolute neutrophil count ≥ 1,500/μL unless there is known hematologic/solid tumor marrow involvement − Platelet count ≥ 75,000/ μL unless there is known marrow involvement of the disease − 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. 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 tumor in liver. − Serum creatinine must be < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute. − Hemoglobin must be ≥ 8g/dL. • Written, voluntarily signed informed consent • Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, must practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent until 6 months after the last doses of BV and until last doses of imatinib, whatever occurs later, or agrees to completely abstain from heterosexual intercourse. • 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 BV, or agrees to completely abstain from heterosexual intercourse.
|
|
E.4 | Principal exclusion criteria |
• Patient has received any other investigational treatment within 28 days before study entry • Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or imatinib • ECOG performance status ≥ 3 • Acute or chronic infections • Female patients who are pregnant or breast-feeding • Known diagnosis of HIV • Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection • Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to the protocol. • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML • Symptomatic neurologic disease compromising normal activities of daily living or requiring medications • Any sensory or motor peripheral neuropathy greater than or equal to Grade 2 • Known history of any of the following cardiovascular conditions o Myocardial infarction within 2 years of study entry o New York Heart Association (NYHA) Class III or IV heart failure o 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 o Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50% • Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose • Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 72 month, at end of study after LVLP |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
after 72 month, at end of study after LVLP |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last patient last visit. (6 years after inclusion of first patient) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |