PK Study on Ready-to-Use Injection (VSLI-RTU) 1 Vial & 3 Vial Formulation Marqibo® in Hematological Malignant Patients
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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):
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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.
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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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: 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. |
Drug: Vincristine Sulfate Liposome
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.
Other Names:
Combination Product: CHOP
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)
Other Names:
Combination Product: R-CHOP
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)
Other Names:
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Experimental: 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. |
Drug: Vincristine Sulfate Liposome
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.
Other Names:
Combination Product: CHOP
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)
Other Names:
Combination Product: R-CHOP
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)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- PK analysis Area under the concentration time curve (AUC) [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.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Patient has a hematological malignancy and is eligible to receive CHOP or R-CHOP regimen.
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Patient must have adequate hematological, renal, and hepatic function as specified below within 30 days prior to the first dose of study treatment:
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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:
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Patient has severe neurologic disorders (Grade 3 and above) including peripheral motor and sensory, central and autonomic neuropathy.
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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.
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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.
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Patient has bowel obstruction, paralytic ileus, or uncontrolled chronic constipation.
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Patient has severe, active and uncontrolled hepatic disease or dysfunction.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Acrotech Biopharma LLC
- Axis Clinicals Limited
Investigators
- Study Director: Wasim Khan, MD, Acrotech Biopharma LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SPI-MAR-101