Phase II Study of Folotyn With Leucovorin to Prevent/Reduce Mucositis in Patients With Hematological Malignancies

A Phase 2, Single-Arm, Open-Label, Multicenter, Study of Folotyn® (Pralatrexate Injection) in Combination With Oral Leucovorin to Prevent or Reduce Mucositis in Patients With Hematological Malignancies Including PTCL and CTCL

This study is to evaluate the effect of leucovorin in preventing or reducing Folotyn-related Grade 2 or higher oral mucositis.

This is a Phase 2, single-arm, open-label, multicenter study to determine the effect of leucovorin in preventing or reducing Folotyn-related Grade 2 or higher oral mucositis in patients with hematological malignancies including PTCL and CTCL.

Patients with hematological malignancies, including PTCL and CTCL, will be enrolled based on meeting all protocol eligibility criteria. The primary endpoint will be evaluated in the first 7-week treatment cycle. For patients who respond to study treatment, the Investigator can treat patients for a total of 6 cycles. Approximately 37 patients will be enrolled. Safety, as assessed by reported SAEs, will continue to be monitored during the optional treatment period. Efficacy will be followed to the extent that it is evaluated according to the Institution's standard of care. No formal analysis of efficacy will be made.

Inclusion Criteria:

1. Patient is diagnosed with hematological malignancies including PTCL and CTCL and are eligible for treatment with a dose of 30 mg/m^2

2. Patient is at least 18 years of age

3. Patient has been informed of the investigational nature of this study and has given written Informed Consent and is able to adhere to dosing and visit schedules and meet all study requirements

4. Patient has recovered from the toxic effects of prior therapy, and is at least 30 days from the most recent cytotoxic therapy, prior to enrollment

5. Patient has adequate hematologic, hepatic, and renal function as defined by:

   • ANC ≥1000/µL
   • Platelet count ≥100,000/µL
   • Total bilirubin ≤1.5 mg/dL
   • Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT), and gamma-glutamyltransferase (GGT) ≤2.5 xupper limit of normal (ULN) (AST/ALT/GGT ≤5 xULN if documented hepatic involvement with lymphoma)
   • Creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥50 mL/min

6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2

7. Females of childbearing potential are to agree to practice a medically acceptable contraceptive regimen (including a barrier method) from study treatment initiation until at least 30 days after the last administration of Folotyn or leucovorin, whichever is last, and are to have a negative urine beta human chorionic gonadotropin (β-HCG) pregnancy test within 14 days prior to the first day of study treatment. Females who are postmenopausal for at least 1 year (defined as >12 months since last menses) or are surgically sterilized do not require this test

8. Male patients are to agree to use a barrier method of contraception from study treatment initiation until at least 90 days after the last administration of Folotyn

Exclusion Criteria:

1. Patient has congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification
2. Patient has uncontrolled hypertension
3. Patient has known, uncontrolled human immunodeficiency virus (HIV)-positive diagnosis
4. Patient has symptomatic central nervous system (CNS) metastases or lesions for which treatment is required. Patients who received prophylactic CNS treatment are eligible
5. Patient has an active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the patient to receive protocol treatment
6. Patient has had major surgery within 14 days prior to enrollment
7. Patient has used any investigational drugs, biologics, or devices within 14 days prior to study treatment or plans to use any of these during the course of the study
8. Patient has had previous exposure to Folotyn within 6 months of study enrollment
9. Patient is pregnant or breast-feeding