A study in patients with T-cell lymphoma to look at the effects of a new treatment

• Conditions: Patients with previously undiagnosed peripheral T-cell lymphoma who have achieved an objective response following initial treatment with CHOP-based chemotherapy; MedDRA version: 14.1Level: PTClassification code 10034623Term: Peripheral T-cell lymphoma unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-022230-81-BE
• Lead Sponsor: Allos Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06-14
• Last Update Posted: 17 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 549

Inclusion Criteria

1. Patient’s peripheral T-cell lymphoma(PTCL) histology has been confirmed as one of the following by a 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 complete response 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 x upper limit of normal (ULN), (AST/ALT < 5 x 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. Women 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).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Patient has:
a. Precursor T/NK neoplasms
b. Anaplastic large cell lymphoma (anaplastic lymphoma kinase positive) with International Prognostic Index score < 2 at initial diagnosis and complete response 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. Sézary syndrome
g. Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma 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 peripheral T-cell lymphoma (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 clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Determine the efficacy of pralatrexate compared to observation when administered to patients with previously undiagnosed peripheral T-cell lymphoma (PTCL) who have achieved an objective response after completing at least 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based treatment.;Secondary Objective: Determine the safety of pralatrexate when administered following a course of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based treatment to patients with previously undiagnosed peripheral T-cell lymphoma (PTCL).;Primary end point(s): Progression-free survival and overall survival.;Timepoint(s) of evaluation of this end point: Progression-free survival and overall survival - assessed throughout the period of the study.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Objective response (complete response [CR] or partial response [PR]) to pralatrexate versus observation;Timepoint(s) of evaluation of this end point: Objective response (complete response [CR] or partial response [PR]) to pralatrexate versus observation - response assessment to occur at 8 weeks, then every 12 weeks (± 1 week) through 3 years post-randomization, then every 24 weeks through 7 years post-randomization.