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
- Conditions
- -C844 Peripheral T-cell lymphoma, not classifiedPeripheral T-cell lymphoma, not classifiedC844
- Registration Number
- PER-035-13
- Lead Sponsor
- Spectrum Pharmaceuticals, Inc. (antes Allos Therapeutics, Inc.),
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Sex
- Not specified
- Target Recruitment
- 0
1. Patient’s PTCL histology has been confirmed as one of the following by an independent pathology reviewer, using the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification:
a. T/natural killer (NK)-cell leukemia/lymphoma
b. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)
c. Angioimmunoblastic T-cell lymphoma
d. Anaplastic large cell lymphoma (ALCL), primary systemic type, excluding anaplastic lymphoma kinase positive (ALK+) with International Prognostic Index (IPI) score < 2 at initial diagnosis and CR after completion of CHOP-based therapy
e. PTCL-unspecified
f. Enteropathy-type intestinal lymphoma
g. Hepatosplenic T-cell lymphoma
h. Subcutaneous panniculitis T-cell lymphoma
i. Transformed mycosis fungoides
j. Extranodal T/NK-cell lymphoma nasal or nasal type
k. Primary cutaneous gamma-delta T-cell lymphoma
l. Primary cutaneous CD8+ aggressive epidermic cytotoxic T-cell lymphoma
2. Documentation that the patient has completed at least 6 cycles of CHOP-based therapy, including:
a. CHOP 21
b. CHOP 14
c. CHOEP
d. Other CHOP variants: includes all 4 components of CHOP represented, with substitution allowed for any 1 component with a drug of the same mechanism of action (eg, variant anthracyclines). Additional components to CHOP are allowed, with the exception of alemtuzumab; rituximab may be combined with CHOP provided that it is not given within 3 cycles of randomization.
3. Patient has achieved a CR or PR per investigator’s assessment following completion of CHOP-based therapy and has had a radiological assessment within 21 days prior to randomization.
4. ≥ 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. Adequate hematological, hepatic, and renal function as defined by:
a. Absolute neutrophil count (ANC) ≥ 1000/μL
b. Platelet count ≥ 100,000/μL
c. Total bilirubin ≤ 1.5 mg/dL
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 upper limit of normal (ULN), (AST/ALT < 5 ULN if documented hepatic involvement with lymphoma). All patients with hepatitis B virus (HBV)-positive serology must have liver function tests within the above parameters.
e. Creatinine ≤ 1.5 mg/dL (if the patient’s creatinine is > 1.5 mg/dL, then the calculated creatinine clearance must be ≥ 50 mL/min).
7. Females of childbearing potential (ie, excluding patients who are postmenopausal for at least 1 year [> 12 months since last menses] or are surgically sterilized) must:
a. Have a negative serum pregnancy test within 14 days prior to randomization and
b. Agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate.
8. Males 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.
9. Patient has given written informed consent (IC)
. Patient has:
a. Precursor T/NK neoplasms
b. ALCL (ALK+) with IPI score < 2 at initial diagnosis and CR after completion of CHOP-based therapy
c. T-cell prolymphocytic leukemia (T-PLL)
d. T-cell large granular lymphocytic leukemia
e. Mycosis fungoides, other than transformed mycosis fungoides
f. Sezary syndrome
g. Primary cutaneous CD30+ disorders: ALCL and lymphomatoid papulosis
2. If there is a history of prior malignancies other than those exceptions listed below, the patient must be disease-free for 5 years. Patients with the following prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease.
a. Non-melanoma skin cancer
b. Carcinoma in situ of the cervix
c. Localized prostate cancer
d. Localized thyroid cancer
3. Patient has received prior treatment (chemotherapy or radiation) for PTCL, other than a single allowed CHOP regimen, with the exception of:
a. Patients with nasal NK lymphoma are permitted to have received local radiation therapy no less than 4 weeks prior to randomization.
b. Patients with transformed mycosis fungoides are permitted to have received 1 systemic single-agent chemotherapy (other than methotrexate) prior to transformation of their disease.
4. Prior exposure to pralatrexate.
5. Receipt of systemic corticosteroids within 3 weeks of study treatment, unless patient has been taking a continuous dose of ≤ 10 mg/day of oral prednisone or equivalent for at least 4 weeks or as part of a CHOP prednisone taper.
6. Planned use of any treatment for PTCL during the course of the study.
7. Patient has:
a. Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of < 100 mm3 or detectable viral load within past 3 months and is receiving anti-retroviral therapy.
b. HBV-positive serology and is receiving interferon therapy or has liver function test results outside the parameters of study inclusion criteria. Patients are permitted to receive other antiviral therapies if the therapy has been administered at a stable dose for ≥ 4 weeks.
c. Hepatitis C virus (HCV) with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.
d. Symptomatic central nervous system (CNS) metastases or lesions for which treatment is required.
e. Uncontrolled hypertension or congestive heart failure Class III/IV according to the New York Heart Association’s Heart Failure Guidelines (see http://www.americanheart.org/presenter.jhtml?identifier=3065080).
f. Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness that would impair the ability of the patient to receive protocol treatment.
8. Patient has had major surgery within 2 weeks prior to study entry; other than for line placement or biopsy procedure.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method