E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma |
|
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] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 assess the antitumor efficacy of single-agent brentuximab vedotin (1.8 mg/kg administered intravenously every 3 weeks) as measured by the overall objective response rate (ORR) in
patients with relapsed or refractory sALCL following at least 1 multiagent chemotherapy (CHOP or equivalent multiagent chemotherapy regimens with curative intent) |
|
E.2.2 | Secondary objectives of the trial |
To determine duration of tumor control, including duration of response, progression-free survival, and complete remission rate with brentuximab vedotin.
To determine the percentage of patients receiving hematopoietic stem cell transplant (either autologous or allogeneic) after brentuximab vedotin therapy.
To determine overall survival with brentuximab vedotin.
To assess the safety and tolerability of brentuximab vedotin.
To assess the pharmacokinetics of brentuximab vedotin.
To determine the immunogenicity of brentuximab vedotin. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with relapsed or refractory sALCL who have previously received at least 1 multiagent chemotherapy (CHOP or equivalent multiagent chemotherapy regimen with curative intent).
- Histologically-confirmed sALCL based on local pathology report. If archived tissue cannot be obtained, a biopsy should be performed at screening.
- Age greater than or equal to 18 years.
- Patients must have bidimensional measurable disease of ≥ 1.5 cm as documented by radiographic technique (spiral CT preferred) per the International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma. |
|
E.4 | Principal exclusion criteria |
1. Previous treatment with brentuximab vedotin.
2. Previously received an allogeneic transplant.
3. Patients with current diagnosis of primary cutaneous ALCL (patients whose ALCL has transformed to sALCL are eligible).
4. Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug:
• Myocardial infarction within 6 months before the first dose of
study drug
• 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
5. History of another primary malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limits: nonmelanoma skin cancer, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear.
6. Any active uncontrolled systemic viral, bacterial, or fungal infection
7. Any antimicrobial, antiviral, or antifungal therapy within 1 week prior to the first dose of brentuximab vedotin (routine prophylaxis is acceptable)
8. Treatment with any investigational products within 4 weeks before the first dose of study drug
9. Current therapy with other systemic anti-neoplastic or investigational agents.
10. Known cerebral/meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy (PML).
11. Female patients who are lactating and breastfeeding or have a positive serum or urine pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug.
12. Patients with dementia or an altered mental state that would preclude the understanding and rendering of informed consent.
13. Known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation.
14. Known human immunodeficiency virus (HIV) positive.
15. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) per independent review facility
(IRF) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Screening
- At the End of Treatment Visit: 30 days after last dose of study drug
- During the follow up period: Every 3 months for 18 months from EOT or until the sooner of disease progression, death or study closure.Overall survival data will be collected every 3 months from EOT for 18 months, then every 6 months thereafter until the sooner of death or study closure.
|
|
E.5.2 | Secondary end point(s) |
- Duration of response per IRF
- Progression-free survival (PFS) per IRF
- Complete remission (CR) rate per IRF
- Percentage of patients receiving hematopoietic stem cell transplant (SCT) following treatment with brentuximab vedotin
- Overall survival (OS)
- Type, incidence, severity, seriousness, and relatedness of adverse events, and laboratory abnormalities
- Selected pharmacokinetic parameters
- The presence of anti-therapeutic antibodies (ATA) to brentuximab vedotin |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints will be evaluated at the end of trial visit. |
|
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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, Serum Biomarkers |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |