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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hematologic Diseases

Intervention / Treatment
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* Drug: Vincristine Sulfate Liposome
* Combination Product: CHOP
* Combination Product: R-CHOP


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>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<br>* 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.<br>* Other names: Marqibo;Combination Product: CHOP<br>* 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)<br>* Other names: Adriamycin, (Oncovin);Combination Product: R-CHOP<br>* 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)<br>* Other names: cyclophosphamide. doxorubicin, vincristine , prednisone + Rituximab;|
| Experimental: Cohort B<br>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<br>* 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.<br>* Other names: Marqibo;Combination Product: CHOP<br>* 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)<br>* Other names: Adriamycin, (Oncovin);Combination Product: R-CHOP<br>* 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)<br>* Other names: cyclophosphamide. doxorubicin, vincristine , prednisone + Rituximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK analysis Area under the concentration time curve (AUC) | To evaluate the serum pharmacokinetics (PK) of the 1-vial VSLI-RTU formulation versus the current Marqibo 3-vial formulation for intravenous (IV) injection. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematology, Hematological Malignancy, CHOP, R-CHOP