PK Study on Ready-to-Use Injection (VSLI-RTU) 1 Vial & 3 Vial Formulation Marqibo® in Hematological Malignant Patients

An Open-Label, Randomized, Pharmacokinetic Study of vinCRIStine Sulfate LIPOSOME Injection Ready-to-Use (VSLI-RTU) Formulation (1-Vial) and Marqibo® Formulation (3-Vials) in Patients With Hematological Malignancies

This is a Phase 1, randomized, open-label, 2-way crossover, pharmacokinetic study in adult patients with hematological malignancies eligible to receive either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen or rituximab-CHOP (R-CHOP) regimen.

Eligible patients will be randomized in a 1:1 ratio to one of 2 treatment cohorts (Cohorts A or B) in which the Marqibo formulation and the 1-vial VSLI-RTU formulation of vincristine are administered in a 2-way crossover design over 2 treatment cycles (21 days each):

• Cohort A: Marqibo formulation given at a dose of 2.25 mg/m2 with no dose cap during Cycle 1, and VSLI-RTU formulation given at 2.25 mg/m2 with no dose cap during Cycle 2.
• Cohort B: VSLI-RTU formulation given at a dose of 2.25 mg/m2 with no dose cap during Cycle 1 and Marqibo formulation given at 2.25 mg/m2 with no dose cap during Cycle 2.

Both formulations of vincristine sulfate LIPOSOME injection will be administered via a 60 (±10) minute IV infusion.

Blood samples for PK evaluation will be drawn at the following time points: immediately before infusion, 0.5 hour after the start of the infusion, 0.5 hour after the end of infusion (EOI), and 3, 8, 15, 24, 48, 72, and 96 hours post-EOI.

In addition to Marqibo or VSLI-RTU, all patients will receive standard doses (per institutional or regional guidelines) of cyclophosphamide, prednisone, and doxorubicin, (and rituximab if patient is on the R-CHOP regimen), on Day 1 and prednisone (or prednisolone if consistent with institutional or regional guidelines) on Days 2 to 5.

Key Inclusion Criteria:

• Patient has a hematological malignancy and is eligible to receive CHOP or R-CHOP regimen.
• Patient must have adequate hematological, renal, and hepatic function as specified below within 30 days prior to the first dose of study treatment:
• Patient has a left ventricular ejection fraction ≥50% by multigated acquisition scan or echocardiogram within 30 days prior to the first dose of study treatment.

Key Exclusion Criteria:

• Patient has severe neurologic disorders (Grade 3 and above) including peripheral motor and sensory, central and autonomic neuropathy.
• Patient has a history of persistent active neurologic disorders including the demyelinating form of Charcot-Marie-Tooth syndrome, acquired demyelinating disorders, and other demyelinating conditions.
• Patient has used any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study.
• Patient has bowel obstruction, paralytic ileus, or uncontrolled chronic constipation.
• Patient has severe, active and uncontrolled hepatic disease or dysfunction.