Overview

This trial is active, not recruiting.

Conditions relapsed peripheral t-cell lymphoma, refractory peripheral t-cell lymphoma
Treatments alisertib, pralatrexate, gemcitabine, romidepsin
Phase phase 3
Targets ARK-1, HDAC
Sponsor Millennium Pharmaceuticals, Inc.
Start date June 2012
End date November 2016
Trial size 271 participants
Trial identifier NCT01482962, 2011-003545-18, C14012, DRKS00004503, NL39566.068.12, U1111-1181-8218

Summary

This is a phase 3, randomized, 2-arm, open-label, international trial evaluating alisertib compared with single-agent treatment, as selected by the investigator from the offered options of pralatrexate or gemcitabine or romidepsin, in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Note: romidepsin will not be used as a single-agent comparator in countries that do not permit its use at this time.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Alisertib
alisertib
Patients randomized to receive alisertib will be administered an enteric-coated tablet formulation 5×10-mg twice daily orally for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle.
(Active Comparator)
Pralatrexate,or Romidepsin,or Gemcitabine
pralatrexate
Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate,or Romidepsin, or Gemcitabine. Patients randomized to receive Pralatrexate will be administered the drug at 30mg/m2 as an intravenous (IV) push over 3 to 5 min once weekly for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles should be repeated every 7 weeks
gemcitabine
Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate, or Romidepsin, or Gemcitabine. Patients randomized to receive Gemcitabine will receive the drug intravenously at 1,000 mg/m2 over 30 minutes on Days 1, 8, and 15 of a 28-day cycle. Cycles should be repeated every 28 days in the absence of disease progression or unacceptable toxicity.
romidepsin
Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate, or Romidepsin, or Gemcitabine. Patients randomized to receive Romidepsin will be administered the drug intravenously at 14mg/m2 over a 4-hour period on Days 1,8,& 15 of a 28-cycle. Cycles should be repeated every 28 days.

Primary Outcomes

Measure
Number of patients with overall response
time frame: Change from screening period in response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Number of patients with PFS
time frame: Change from screening period in response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years

Secondary Outcomes

Measure
Number of patients with complete response + complete response unconfirmed
time frame: Response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Number of patients with overall survival
time frame: Patients will be followed for survival for 2 years from date of last patient off study, or death, whichever occurs first. Contacts will be every 4 months.
Time to disease progression, duration of response, and time to response
time frame: At the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years.
Number of adverse events, serious adverse events, assessments of clinical laboratory values and clinically important abnormalities, and vital sign measurements
time frame: For each patient, from screening period to 30 days after last dose of study drug, approximately 1 year
Time to subsequent antineoplastic therapy
time frame: From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years
Plasma concentration-time data to contribute to future population pharmacokinetics (PK) analysis
time frame: Cycle 1, Days 1&7; Cycle 2, Day 8; Cycle 3, Day 8; Cycle 4, Day 8. Duration approximately 4 months.
Changes in reported symptoms and Quality of Life (QOL) assessment per Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) for functioning and symptoms
time frame: At screening period; Day 1 of each cycle; End of Treatment; Progression Free Survival follow-up. Duration approximately 3 years.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female patients age 18 or older - Patients with PTCL according to World Health Organization (WHO) criteria 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 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 all of the 3 comparator drugs (pralatrexate, or romidepsin or 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% - 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 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

Additional Information

Official title A Phase 3, Randomized, Two-Arm, Open-Label, Multicenter, International Trial of Alisertib (MLN8237) or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Takeda.