Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma

Millennium Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Refractory Peripheral T-Cell Lymphoma; Relapsed Peripheral T-Cell Lymphoma

Treatments: Drug: Pralatrexate; Drug: Gemcitabine; Drug: Alisertib; Drug: Romidepsin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01482962

NL39566.068.12 (Registry Identifier)

2011-003545-18 (EudraCT Number)

C14012

U1111-1181-8218 (Registry Identifier)

DRKS00004503 (Registry Identifier)

Details and patient eligibility

About

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 participants with relapsed or refractory peripheral T-cell lymphoma (PTCL). Note: romidepsin was not used as a single-agent comparator outside the United States of America (USA) as supply was not available.

Full description

The drug being tested in this study was Alisertib. Alisertib was tested to treat people who have relapsed/refractory peripheral T-cell lymphoma (PTCL).

This study evaluated alisertib for the improvement in overall response rate (ORR) compared with single-agent treatment, as selected by the investigator from the offered options of pralatrexate, romidepsin (US only), or gemcitabine, in participants with relapsed or refractory PTCL.

The study enrolled 271 patients. Participants were randomized (1:1) to one of 2 treatment arms:

• Alisertib
• Investigator's choice (Pralatrexate, Romidepsin, or Gemcitabine)

This multi-center trial was conducted worldwide. The overall time to participate in this study was approximately 5 years. Participants made multiple visits to the clinic, and then were contacted by telephone up to 42-months after the last participant was randomized, or until death, for follow-up assessment.

Enrollment: 271 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Male or female participants age 18 or older
• Participants with Peripheral T cell lymphoma (PTCL) (selected subtypes) according to World Health Organization (WHO) criteria and have relapsed or are refractory to at least 1 prior systemic, cytotoxic therapy for PTCL. Participants must have received conventional therapy as a prior therapy. Cutaneous-only disease is not permitted. Participants must have documented evidence of progressive and measurable disease.
• Tumor biopsy available for central hematopathologic review
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Female participants 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 participants 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
• Participants 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
• Participants 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 participant must have recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≤ 1 toxicity, to participant'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 participants 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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271 participants in 2 patient groups

Alisertib

Experimental group

Description:

Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).

Treatment:

Drug: Alisertib

Pralatrexate, or Romidepsin, or Gemcitabine

Active Comparator group

Description:

Pralatrexate 30 mg/m\^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m\^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m\^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).

Treatment:

Drug: Romidepsin

Drug: Gemcitabine

Drug: Pralatrexate