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
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.