Primary:* 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…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's T-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
ORR: CR + PR based on independent review committee (IRC) assessment using the
IWG criteria.
PFS based on IRC assessment using the IWG criteria.
Secondary outcome
The key secondary endpoints are:
* CR rate
* 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
* 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
Background summary
Aggressive peripheral T-cell lymphomas (PTCL) are rare malignancies and a
biologically heterogeneous group of lymphomas. The majority of lymphoma
treatments have been developed from studies dominated by the B cell lymphomas,
resulting in approved indications for NHL which are not optimal for PTCL.
Initial treatments usually include a CHOP-based (cyclophosphamide, doxorubicin,
vincristine, and prednisolone) regimen; however, even if a response is
achieved, early relapse is common, and each subtype is associated with a
varying prognosis. There is no consensus on standard treatment for this disease
in the first-line setting and in the second-line setting outside of the US, and
the available treatments are not optimal. Given the aggressive nature of this
disease and with the poorest prognosis of all the NHL subtypes, PTCL patients
represent an unmet medical need.
Alisertib is a selective small-molecule inhibitor of Aurora A kinase that is
being developed for the treatment of advanced malignancies. Alisertib has
demonstrated activity against a variety of nonclinical solid tumor and
hematological malignancy models grown in vitro and in vivo. Multiple responses
have been reported by objective criteria in patients with solid tumors, AML,
and lymphomas who have received alisertib to date. In Study C14004, a phase 2,
single-arm, multicenter study of alisertib in patients with aggressive forms of
relapsed or refractory non-Hodgkin*s B- or T-cell lymphoma, 13 of the 48
enrolled patients achieved a response (ORR of 27%: 5 CR, 8 PR).
Study objective
Primary:
* 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
Key Secondary:
* To determine if alisertib improves CR rate
* To determine if alisertib improves overall survival (OS)
Other Secondary:
* To evaluate the safety and tolerability of alisertib in patients with
relapsed or refractory PTCL
* 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
(FACT-Lym) for functioning and symptoms
Study design
Phase 3, randomized, 2-arm, open-label, multicenter, international trial
evaluating alisertib compared with single-agent treatment, as selected by the
investigator from the offered options of pralatrexate or gemcitabine, in
patients with relapsed or refractory PTCL.
Patients will be randomized (1:1) to study treatment, Arm A (alisertib) or Arm
B (selected single-agent comparator: pralatrexate or gemcitabine).
Intervention
Patients will be randomized (1:1) to study treatment, Arm A (alisertib) or Arm
B (selected single-agent comparator: pralatrexate or gemcitabine).
Study burden and risks
There is no consensus on standard treatment for PTCL and available treatments
are not optimal. In previous studies where patients have been treated with
alisertib, adverse events were generally reversible, dose-dependent, and
consistent with the mechanism of alisertib. Alisertib shows encouraging early
results. During this study, the patients are evaluated frequently while they
are receiving treatment for their safety.
Landsdowne St 40
Cambridge, MA 02139
US
Landsdowne St 40
Cambridge, MA 02139
US
Listed location countries
Age
Inclusion criteria
1. Male or females, age * 18 years
2. Patients with PTCL according to WHO criteria and have relapsed or are refractory to at least 1 prior systemic, cytotoxic therapy for PTCL. Patients must have received conventional therapy as a prior therapy (ie, experimental therapy may not be the only prior therapy). Cutaneous-only disease is not permitted. Patients must have documented evidence of progressive disease
3. Tumor biopsy available for central hematopathologic review
4. Measurable disease according to the IWG criteria (See Section 15.4). Patients must have at least 1 site of disease measurable in 2 dimensions by computed tomography (CT)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;Please see protocol for all inclusion criteria
Exclusion criteria
1. Known central nervous system (CNS) lymphoma
2. Systemic antineoplastic therapy, immunotherapy, investigational agent, or radiation therapy within 4 weeks of first dose of study treatment (6 weeks if nitrosoureas given) or concomitant use during study
3. Prior administration of an Aurora A kinase-targeted agent, including alisertib
4. Prior administration (whether in combination or as single-agent) of all 3 of the comparator drugs for the disease under study: pralatrexate, romidepsin, and gemcitabine;Please see protocol for all exclusion criteria
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-003545-18-NL |
| ClinicalTrials.gov | NCT01482962 |
| CCMO | NL39566.068.12 |