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

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.

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.

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.

Eligible patients will be randomized in a 1:1 ratio to one of 2 treatment cohorts (Cohorts A or B) to receive either the first cycle of treatment with the VSLI-RTU formulation or the Marqibo formulation and crossover to the other formulation for the second cycle.

CHOP to be administered on Day 1 on Cycle 1 & 2 ( 21-day Cycle) & prednisone administration on Days 2 to 5 on Cycle 1 & 2 ( 21-day Cycle)

R-CHOP to be administered on Day 1 on Cycle 1 & 2 ( 21-day Cycle) & prednisone administration on Days 2 to 5 on Cycle 1 & 2 ( 21-day Cycle)

To evaluate the serum pharmacokinetics (PK) of the 1-vial VSLI-RTU formulation versus the current Marqibo 3-vial formulation for intravenous (IV) injection.

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.