Phase 1 Study of Fusilev to Prevent or Reduce Mucositis in Patients With Non-Hodgkin's Lymphoma Receiving Folotyn

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is determine the optimal dose and schedule of Fusilev to prevent or reduce Mucositis in patients with Non-Hodgkin's Lymphoma receiving Folotyn treatment.

Detailed Description
-----------------
This is an open label, uncontrolled, nonrandomized, multicenter, dose finding, Phase 1 study primarily to determine the optimal dose and schedule of Fusilev to prevent or reduce Folotyn-related Grade 3 or higher oral Mucositis.

Official Title
-----------------
An Open Label, Multicenter, Dose Finding, Phase 1 Study of Fusilev® (Levoleucovorin) to Prevent or Reduce Mucositis in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma Receiving Folotyn® (Pralatrexate)

Conditions
-----------------
Non Hodgkin's Lymphoma

Intervention / Treatment
-----------------
* Drug: Fusilev
* Drug: Folotyn


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At least 18 years of age Patients with relapsed or refractory NHL who are eligible for Folotyn treatment. Patient has histologically/cytologically confirmed, measurable (lesion or node ≥ 2 cm by computed tomography [CT] Progressive disease or persistent disease after at least 1 prior treatment ECOG performance status ≤ 2 Adequate hematological, hepatic, and renal function Exclusion Criteria: Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix) Congestive heart failure Uncontrolled hypertension Known human immunodeficiency virus (HIV)-positive diagnosis Active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the patient to receive protocol treatment Major surgery within 14 days of enrollment Pregnant or breast-feeding women Symptomatic central nervous system (CNS) metastases or lesions for which treatment is required. Patients who received prophylactic CNS treatment are eligible Previous exposure to pralatrexate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Fusilev - 10 doses<br>Fusilev: 5 mg/m2 QID, starting on Day 2 (24 ± 3 hours after Folotyn dose) for a total of 10 doses Day 2: 4 doses Day 3: 4 doses Day 4: 2 doses. Folotyn: 30 mg/m2 once weekly for 6 weeks | Drug: Fusilev<br>* Fusilev will be administered by IV push (3-5 minutes) at a dose of 5 mg/m2. Fusilev administration, QID or BID will start 24 ± 3 hours after Folotyn administration depending on the dose cohort.<br>* Other names: Fusilev - (Levoleucovorin);Drug: Folotyn<br>* A cycle of Folotyn treatment is 7 weeks, 6 weeks of treatment followed by 1 week of rest.<br>* Other names: Folotyn - (Pralatrexate);|
| Experimental: Cohort 2: Fusilev - 6 doses<br>Fusilev: 5 mg/m2 BID, on Days 2 (24 ± 3 hours after Folotyn dose), 3, and 4. Folotyn: 30 mg/m2 once weekly for 6 weeks | Drug: Fusilev<br>* Fusilev will be administered by IV push (3-5 minutes) at a dose of 5 mg/m2. Fusilev administration, QID or BID will start 24 ± 3 hours after Folotyn administration depending on the dose cohort.<br>* Other names: Fusilev - (Levoleucovorin);Drug: Folotyn<br>* A cycle of Folotyn treatment is 7 weeks, 6 weeks of treatment followed by 1 week of rest.<br>* Other names: Folotyn - (Pralatrexate);|
| Experimental: Cohort 3: Fusilev - 4 doses<br>5 mg/m2 BID, on Days 2 (24 ± 3 hours after Folotyn dose) and 3. Folotyn: 30 mg/m2 once weekly for 6 weeks | Drug: Fusilev<br>* Fusilev will be administered by IV push (3-5 minutes) at a dose of 5 mg/m2. Fusilev administration, QID or BID will start 24 ± 3 hours after Folotyn administration depending on the dose cohort.<br>* Other names: Fusilev - (Levoleucovorin);Drug: Folotyn<br>* A cycle of Folotyn treatment is 7 weeks, 6 weeks of treatment followed by 1 week of rest.<br>* Other names: Folotyn - (Pralatrexate);|
| Experimental: Cohort 4: Fusilev - 2 doses<br>5 mg/m2 BID, on Day 2 (24 ± 3 hours after Folotyn dose. Folotyn: 30 mg/m2 once weekly for 6 weeks | Drug: Fusilev<br>* Fusilev will be administered by IV push (3-5 minutes) at a dose of 5 mg/m2. Fusilev administration, QID or BID will start 24 ± 3 hours after Folotyn administration depending on the dose cohort.<br>* Other names: Fusilev - (Levoleucovorin);Drug: Folotyn<br>* A cycle of Folotyn treatment is 7 weeks, 6 weeks of treatment followed by 1 week of rest.<br>* Other names: Folotyn - (Pralatrexate);|
| Experimental: Cohort 5: Fusilev - 1 dose<br>Fusilev: 5 mg/m2 once on Day 2. Folotyn: 30 mg/m2 once weekly for 6 weeks | Drug: Fusilev<br>* Fusilev will be administered by IV push (3-5 minutes) at a dose of 5 mg/m2. Fusilev administration, QID or BID will start 24 ± 3 hours after Folotyn administration depending on the dose cohort.<br>* Other names: Fusilev - (Levoleucovorin);Drug: Folotyn<br>* A cycle of Folotyn treatment is 7 weeks, 6 weeks of treatment followed by 1 week of rest.<br>* Other names: Folotyn - (Pralatrexate);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal dose and schedule of Fusilev to prevent or reduce mucositis | The patient will be seen in the clinic for an oral mucositis assessment at baseline. During the 6 weeks of Folotyn treatment, oral mucositis assessment will be performed weekly prior to each Folotyn dose and again on Day 4 (prior to the Fusilev dose when applicable) by a qualified health care professional. Patients will complete an Oral Mucositis Daily Questionnaire (OMQD) starting at Day 1 of Week 1 and ending at the End of Treatment Visit. | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Fusilev on Folotyn related Oral Mucositis | To determine the impact of Fusilev on the number of Folotyn-related dose modifications secondary to oral mucositis To determine the impact of Fusilev on the frequency of Folotyn-related oral mucositis To determine the impact of Fusilev on the number of Folotyn doses delivered | 7 weeks | 
| Relationship between Fusilev use and oral mucositis | To determine the relationship between Fusilev use and oral mucositis as a function of the pretreatment homocysteine (HCY) and methylmalonic acid (MMA) levels | 7 weeks |