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
Overview
- Phase
- Phase 1
- Intervention
- Vincristine Sulfate Liposome
- Conditions
- Hematologic Diseases
- Sponsor
- Acrotech Biopharma Inc.
- Enrollment
- 56
- Primary Endpoint
- PK analysis Area under the concentration time curve (AUC)
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
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.
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.
Arms & Interventions
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.
Intervention: Vincristine Sulfate Liposome
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.
Intervention: CHOP
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.
Intervention: R-CHOP
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.
Intervention: Vincristine Sulfate Liposome
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.
Intervention: CHOP
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.
Intervention: R-CHOP
Outcomes
Primary Outcomes
PK analysis Area under the concentration time curve (AUC)
Time Frame: 6 weeks
To evaluate the serum pharmacokinetics (PK) of the 1-vial VSLI-RTU formulation versus the current Marqibo 3-vial formulation for intravenous (IV) injection.