Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients

A Multi-center, Randomized, Phase 3 Study of Sequential Pralatrexate Versus Observation in Patients Previously Undiagnosed Peripheral T-cell Lymphoma Who Achieved an Objective Response After Initial Treatment With CHOP-based Chemotherapy

The purpose of this study is to see if pralatrexate extends response and survival following CHOP-based chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) and if pralatrexate improves response in patients with partial response following CHOP-based chemotherapy. Patients will either receive pralatrexate or be under observation. All patients will receive vitamins B12 and folic acid and attend regular clinic visits to evaluate their disease and health.

This was an international, multi-center, randomized, Phase 3, open-label study of sequential pralatrexate versus observation in patients with previously undiagnosed PTCL who have achieved an objective response following initial treatment with CHOP-based chemotherapy.

Upon documentation of completion of an objective response following at least 6 cycles of a designated CHOP-based chemotherapy confirmation of histopathology by independent review, and confirmation that all eligibility criteria were met, patients were randomized in a 2:1 ratio to either pralatrexate or observation, according to a permuted block design with stratification factor of Tumor Response per Investigator at completion of CHOP-based therapy (Complete Response [CR] vs Partial Response [PR]).

All patients who receive at least 1 dose of pralatrexate were followed for safety through 35 (± 5) days after their last dose of pralatrexate or until all treatment-related AEs have resolved or returned to baseline/Grade 1, whichever is longer, or until it was determined that the outcome does not change with further follow-up.

Inclusion Criteria:

• Patient has one of the following peripheral T-cell lymphoma (PTCL) subtypes confirmed by an independent central pathology reviewer, using the Revised European American Lymphoma World Health Organization disease classification:

  • T/natural killer (NK)-cell leukemia/lymphoma
  • Adult T-cell lymphoma (TCL)/leukemia (human T-cell leukemia virus 1+)
  • Angioimmunoblastic TCL
  • Anaplastic large cell lymphoma (ALCL), primary systemic type, excluding anaplastic lymphoma kinase positive (ALK+) with International Prognostic Index (IPI) score less than 2 at initial diagnosis and complete response (CR) after CHOP-based therapy
  • PTCL-unspecified
  • Enteropathy-type intestinal lymphoma
  • Hepatosplenic TCL
  • Subcutaneous panniculitis TCL
  • Transformed mycosis fungoides (tMF)
  • Extranodal T/NK-cell lymphoma nasal or nasal type
  • Primary cutaneous gamma-delta TCL
  • Primary cutaneous CD8+ aggressive epidermic cytotoxic TCL

• Documented completion of at least 6 cycles of CHOP-based therapy:

  • CHOP 21
  • CHOP 14
  • CHOP + etoposide
  • Other CHOP variants: substitution allowed for 1 component with a drug of the same mechanism of action. Additional components, except alemtuzumab, are allowed. Rituximab may be added if not given within 3 cycles of randomization.

• Patient has achieved CR or partial response (PR) per per investigator's assessment following completion of CHOP-based therapy and has had radiological assessment within 21 days prior to randomization.

• Eastern Cooperative Oncology Group performance status less than or equal to 2.

• Adequate blood, liver, and kidney function as defined by laboratory tests.

• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate.

• Men who are sexually active, including those with a pregnant partner, must agree to practice a medically acceptable barrier method contraceptive regimen (eg, condoms) while receiving pralatrexate and for 90 days after the last administration of pralatrexate.

• Has given written informed consent.

Exclusion Criteria:

• Patient has:

  • Precursor T/NK neoplasms
  • ALCL (ALK+) with IPI score less than 2 at initial diagnosis and CR after CHOP-based therapy
  • T cell prolymphocytic leukemia
  • T cell large granular lymphocytic leukemia
  • Mycosis fungoides, except tMF
  • Sézary syndrome
  • Primary cutaneous CD30+ disorders: ALCL and lymphomatoid papulosis

• If there is a history of prior malignancies other than those below, must be disease free for at least 5 years. Patients with malignancies listed below less than 5 years before study entry may be enrolled if they have received treatment resulting in complete resolution of the cancer and have no clinical, radiologic, or laboratory evidence of active/recurrent disease.

  • non-melanoma skin cancer
  • carcinoma in situ of the cervix
  • localized prostate cancer
  • localized thyroid cancer

• Receipt of prior chemotherapy (CT) or radiation therapy (RT) for PTCL, other than a single allowed CHOP regimen, except:

  • Patients with nasal NK lymphoma who received local RT less than 4 weeks prior to randomization.
  • Patients with tMF who received 1 systemic single-agent CT (except methotrexate) prior to transformation.

• Prior exposure to pralatrexate.

• Receipt of systemic corticosteroids within 3 weeks of study treatment, unless patient has been taking a continuous dose of 10 mg/day or less of oral prednisone or equivalent for at least 4 weeks or as part of a CHOP prednisone taper.

• Planned use of any treatment for PTCL during the course of the study.

• Patient has:

  • Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of less than 100 mm3 or detectable viral load within past 3 months and receiving anti-retroviral therapy.
  • Hepatitis B (HBV)-positive serology and is receiving interferon therapy or has liver function test results outside the parameters of study inclusion criteria. Other antiviral therapies are permitted if at a stable dose for at least 4 weeks.
  • Hepatitis C (HCV) virus with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.
  • Symptomatic central nervous system metastases or lesions requiring treatment.
  • Uncontrolled hypertension or congestive heart failure Class III/IV per the New York Heart Association's Heart Failure Guidelines
  • Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness impairing the ability of the patient to receive protocol treatment.

• Major surgery within 2 weeks prior to study entry, except for line placement or biopsy procedure.