E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Peripheral T-Cell Lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed or Refractory Peripheral T-Cell Lymphoma |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034629 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034628 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified stage II |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034627 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified stage I |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034626 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034630 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034625 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034623 |
E.1.2 | Term | Peripheral T-cell lymphoma unspecified |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 if alisertib improves overall response rate (ORR; complete response [CR] plus partial response [PR]) versus a selection of single agents in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) - To determine if alisertib improves progression free survival (PFS) versus a selection of single agents in patients with relapsed or refractory PTCL |
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E.2.2 | Secondary objectives of the trial |
Key Secondary:
- To determine if alisertib improves overall survival (OS)
Other secondary objectives include:
- To evaluate the safety and tolerability of alisertib in patients with relapsed or refractory PTCL
- To determine if alisertib improves CR rate
- To measure time to disease progression (TTP)
- To determine duration of response
- To measure time to response
- To measure time to subsequent antineoplastic therapy
- To collect pharmacokinetic (PK) data to contribute to population PK analyses
- To evaluate the impact of alisertib treatment versus control on the Quality of Life (QOL) through Functional Assessment of Cancer Therapy
– Lymphoma (FACTLym) for functioning and symptoms |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients age 18 or older - Patients with PTCL according to World Health Organization (WHO) criteria (nodal and extranodal disease subtypes) and have relapsed or are refractory to at least 1 prior systemic, cytoxic therapy for PTCL. Patients must have received conventional therapy as a prior therapy. Cutaneous-only disease is no permitted. Patients must have documented evidence of progressive disease. - Tumor biopsy available for central hematopathologic review - Measurable disease according to the IWG criteria - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 - Female patients who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of study drug or agree to abstain from heterosexual intercourse. - Male patients who agree to practice effective barrier contraception through 6 months after the last dose of alisertib or agree to abstain from heterosexual intercourse - Suitable venous access - Voluntary written consent |
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E.4 | Principal exclusion criteria |
- Known central nervous system lymphoma
- Systemic antineoplastic therapy, immunotherapy, investigational agent or radiation therapy within 4 weeks of first dose of study treatment or concomitant use during study
- Prior administration of an Aurora A kinase-targeted agent, including alisertib; or both of the comparator drugs (pralatrexate, gemcitabine; or known hypersensitivity)
- History of uncontrolled sleep apnea syndrome or other conditions that could result in excessive daytime sleepiness
- Cardiac condition as specified in study protocol, including left ventricular ejection fraction (LVEF) <40%
- Serum potassium < 3.6 mmol/L or serum magnesium < 0.85 mmol/L
- Concomitant use of other medicines as specified in study protocol
- Patients with abnormal gastric or bowel function who require continuous treatment with H2-receptor antagonists or proton pump inhibitors
- Known active and/or chronic infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C
- Autologous stem cell transplant less than 3 months prior to enrollment
- Patients who have undergone allogeneic stem cell or organ transplantation any time
- Inadequate blood levels, bone marrow or other organ function as specified in study protocol
- The patient must have recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≤ 1 toxicity, to patients's baseline status (except alopecia), or deemed irreversible from the effects of prior cancer therapy
- Major surgery, serious infection, or infection requiring systemic antibiotic therapy within 14 days prior to the first dose of study treatment
- Female patients who are breastfeeding or pregnant
- Coexistent second malignancy or history of prior solid organ malignancy within previous 3 years
- Serious medical or psychiatric illness or laboratory abnormality that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are: - ORR: CR + PR based on independent review committee (IRC) assessment using the IWG criteria - PFS based on IRC assessment using the IWG criteria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint for evaluation for all endpoints is anticipated to occur in May 2017 |
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E.5.2 | Secondary end point(s) |
The key secondary endpoints are:
- Overall survival
Other secondary endpoints include:
- Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values and clinically important laboratory abnormalities, and vital sign measurements
- CR
- Time to disease progression
- Duration of response
- Time to response
- Time to subsequent antineoplastic therapy
- Plasma concentration-time data to contribute to future population PK analysis
- Changes in reported symptoms and QOL assessment per FACT-Lym for functioning and symptoms |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint for evaluation for all endpoints is anticipated to occur in May 2017 |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 87 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
Mexico |
Netherlands |
New Zealand |
Peru |
Poland |
Portugal |
Puerto Rico |
Romania |
Russian Federation |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 |