Peripheral T-cell Lymphoma
Conditions
Keywords
Peripheral T-cell Lymphoma, T-cell Lymphoma, Lymphoma, PDX, Pralatrexate, Vitamin B12, Folic acid
Brief summary
Primary • Determine the efficacy of pralatrexate with concurrent vitamin B12 and folic acid supplementation when administered to patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) Secondary * Determine the safety of pralatrexate with concurrent vitamin B12 and folic acid supplementation when administered to patients with relapsed or refractory PTCL * Determine the pharmacokinetic (PK) profile of pralatrexate when administered with vitamin B12 and folic acid supplementation
Detailed description
This is a Phase 2, single arm, non-randomized, open-label, multi-center study designed to evaluate the safety and effectiveness of pralatrexate when administered with vitamin B12 and folic acid supplementation to patients with relapsed or refractory PTCL. Pralatrexate will be given over 3-5 minutes intravenously (IV), which means through a vein. If pralatrexate is tolerated well, the patient will receive IV injections of pralatrexate every week for 6 weeks, followed by 1 week without receiving pralatrexate. These 7 week cycles will be repeated depending on response and tolerability.
Interventions
Pralatrexate 30 mg/m2 via IV push over 3-5 minutes for 6 weeks in a 7 week cycle.
Sponsors
Acrotech Biopharma Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically/cytologically confirmed PTCL, using the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification: 1. T/Natural Killer (T/NK) cell leukemia/lymphoma 2. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus \[HTLV\] 1+) 3. Angioimmunoblastic T cell lymphoma 4. Blastic Natural Killer (NK) lymphoma (with skin, lymph node, or visceral involvement) 5. Anaplastic large cell lymphoma, primary systemic type 6. PTCL - unspecified 7. T/NK-cell lymphoma - nasal 8. Enteropathy-type intestinal lymphoma 9. Hepatosplenic T cell lymphoma 10. Extranodal peripheral T/NK-cell lymphoma - unspecified 11. Subcutaneous panniculitis T-cell lymphoma 12. Transformed mycosis fungoides * Documented progression of disease after at least 1 prior treatment. Patients may not have received experimental therapy as their only prior therapy. Patient has at least 1 biopsy from initial diagnosis or in the relapsed setting to confirm the diagnosis of PTCL. Patient has recovered from the toxic effects of prior therapy. Patients treated with monoclonal antibody therapy may be enrolled regardless of the time frame of the therapy if they have progression of disease. * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. * ≥ 18 years of age. * Adequate hematological, hepatic, and renal function. * Women of childbearing potential must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Patients who are postmenopausal for at least 1 year or are surgically sterilized do not require this test. * Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 90 days after the last administration of pralatrexate. * Patient has given written informed consent.
Exclusion criteria
* Patient has: 1. Precursor T/NK neoplasms, with the exception of blastic NK lymphoma 2. T cell prolymphocytic leukemia (T-PLL) 3. T cell large granular lymphocytic leukemia 4. Mycosis fungoides, other than transformed mycosis fungoides 5. Sézary syndrome 6. Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis * Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease free for greater than or equal to 5 years. * Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure Guidelines. * Uncontrolled hypertension. * Human immunodeficiency virus (HIV)-positive diagnosis and is receiving combination anti-retroviral therapy. * Patient has, or history of, brain metastases or central nervous system (CNS) disease. * Patient has undergone an allogeneic stem cell transplant. * Patient has relapsed less than 75 days from time of an autologous stem cell transplant. * 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. * Major surgery within 2 weeks of study entry. * Receipt of any conventional chemotherapy or radiation therapy (RT) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study. * Receipt of corticosteroids within 7 days of study treatment, unless patient has been taking a continuous dose of no more than 10 mg/day of prednisone for at least 1 month. * Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study. * Previous exposure to pralatrexate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate Per Independent Central Review | Response was assessed at 7 weeks (prior to Cycle 2) and then prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose | Patient response to treatment was determined by independent central review using International Workshop Criteria (IWC). Results present the best overall response. The initial response assessment was scheduled at week 7 (prior to Cycle 2) and then prior to every even-numbered cycle (every 14 weeks) for up to two years after first dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response Per Independent Central Review | Measured from the first day of documented response, assessed at prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose | Calculated only for those pts with an objective response. Pts receiving subsequent therapy (including transplant) before progressive disease (PD) was documented were censored at date of last response assessment obtained prior to subsequent therapy, with a note indicating censoring occurrence & reason. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last evaluable assessment of response. Pts who withdrew from treatment prior to PD or initiation of subsequent therapy without withdrawing consent were followed for disease status when possible. |
| Progression-free Survival Per Independent Central Review | Calculated as the number of days from treatment day 1 to the date of disease progression or death, regardless of cause for up to 2 years after initial dose | Patients (pts) with subsequent therapy prior to PD were censored at date of last response assessment prior to subsequent therapy. Pts who were alive without PD were censored at the date of last assessment of first dose. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last disease assessment or treatment day 1. Pts who withdrew consent from treatment prior to PD without withdrawing consent for follow-up were followed for disease status & survival. Pts who did not have response assessments after baseline were censored at treatment day 1. |
| Overall Survival Per Independent Central Review | Assessed every 14 weeks while on treatment, and after disease progression no less frequently than every 6 months for up to 2 years after first dose. | Calculated as date of death - date of enrollment +1, estimated using the product-limit estimator. Pts who had not died (no record of death) or were lost to follow-up were censored at the date of last contact. Pts who withdrew consent to participate in the study including consent to be followed, were censored on the date of withdrawal. Pts who withdrew from treatment without withdrawing consent were followed for survival status whenever possible. |
Countries
Belgium, Canada, France, Italy, United Kingdom, United States
Participant flow
Recruitment details
Patients were enrolled between 24 August 2006 and 14 April 2008 across 25 study sites, 15 sites in the United States (US), 8 in Europe, and 2 in Canada.
Pre-assignment details
Patients (pts) were required to have at least 10 days of vitamin supplementation during the up to 12 days between enrollment & dosing. Four of the 115 pts enrolled were excluded during this period: 2 did not have an eligible PTCL subtype per central review, 1 had the presence of B-cell lymphoma per the investigator, 1 had progressive disease.
Participants by arm
| Arm | Count |
|---|---|
| Full Population All patients who received at least one dose of pralatrexate | 111 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Survival Follow-up, After Pralatrexate | Pts still in follow-up at data cutoff | 24 |
| Treatment With Pralatrexate | Treatment with pralatrexate ongoing | 4 |
Baseline characteristics
| Characteristic | Full Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 40 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants |
| Age, Continuous | 57.7 years STANDARD_DEVIATION 15 |
| Region of Enrollment Canada | 9 participants |
| Region of Enrollment Europe | 26 participants |
| Region of Enrollment United States | 76 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 111 / 111 |
| serious Total, serious adverse events | 50 / 111 |
Outcome results
Primary
Response Rate Per Independent Central Review
Patient response to treatment was determined by independent central review using International Workshop Criteria (IWC). Results present the best overall response. The initial response assessment was scheduled at week 7 (prior to Cycle 2) and then prior to every even-numbered cycle (every 14 weeks) for up to two years after first dose.
Time frame: Response was assessed at 7 weeks (prior to Cycle 2) and then prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose
Population: Analysis was per protocol and was based on number of patients (pts) who responded in the evaluable population. The evaluable population consisted of all pts who received at least one dose of pralatrexate and had an eligible peripheral T-cell lymphoma (PTCL) histopathological subtype confirmed by central pathology review.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evaluable Population | Response Rate Per Independent Central Review | 32 of Patients who Responded |
Secondary
Duration of Response Per Independent Central Review
Calculated only for those pts with an objective response. Pts receiving subsequent therapy (including transplant) before progressive disease (PD) was documented were censored at date of last response assessment obtained prior to subsequent therapy, with a note indicating censoring occurrence & reason. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last evaluable assessment of response. Pts who withdrew from treatment prior to PD or initiation of subsequent therapy without withdrawing consent were followed for disease status when possible.
Time frame: Measured from the first day of documented response, assessed at prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose
Population: Analysis was per protocol. Based on the number of responding pts (n=32) in the evaluable population (n=109), as assessed by independent central review protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Evaluable Population | Duration of Response Per Independent Central Review | 306 Days |
Secondary
Overall Survival Per Independent Central Review
Calculated as date of death - date of enrollment +1, estimated using the product-limit estimator. Pts who had not died (no record of death) or were lost to follow-up were censored at the date of last contact. Pts who withdrew consent to participate in the study including consent to be followed, were censored on the date of withdrawal. Pts who withdrew from treatment without withdrawing consent were followed for survival status whenever possible.
Time frame: Assessed every 14 weeks while on treatment, and after disease progression no less frequently than every 6 months for up to 2 years after first dose.
Population: Analysis was per protocol, based on the number of patients (pts) who had an event (death or censoring) at the time of data cut-off.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Evaluable Population | Overall Survival Per Independent Central Review | 14.5 Months |
Secondary
Progression-free Survival Per Independent Central Review
Patients (pts) with subsequent therapy prior to PD were censored at date of last response assessment prior to subsequent therapy. Pts who were alive without PD were censored at the date of last assessment of first dose. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last disease assessment or treatment day 1. Pts who withdrew consent from treatment prior to PD without withdrawing consent for follow-up were followed for disease status & survival. Pts who did not have response assessments after baseline were censored at treatment day 1.
Time frame: Calculated as the number of days from treatment day 1 to the date of disease progression or death, regardless of cause for up to 2 years after initial dose
Population: Analysis was per protocol, based on the number of patients (pts) who had an event of progressive disease (PD) or death. Pts who did not have an event at the time of data cut-off were censored. Pts were censored for lack of PD, receipt of other anti-cancer therapy before PD, termination of study/follow-up for response, and transplant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Evaluable Population | Progression-free Survival Per Independent Central Review | 106 Days |