A Multi-center, Randomized, Phase 3 Study of Sequential Pralatrexate Versus Observation in Patients With Previously Undiagnosed Peripheral T-cell Lymphoma Who Have Achieved an Objective Response Following Initial Treatment With CHOP-based Chemotherapy
- 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
- 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
- Has given written informed consent.
- Patient has:
- Precursor T/NK neoplasms
- ALCL (ALK+) with IPI score less than 2 at initial diagnosis and CR after
- 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
- 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
- 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
- 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