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

Phase 1

• Conditions: Hematologic Diseases
• Interventions: Drug: Vincristine Sulfate Liposome; Combination Product: CHOP; Combination Product: R-CHOP

• Registration Number: NCT04243434
• Lead Sponsor: Acrotech Biopharma Inc.

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.

Study Timeline

• Study First Submitted: 2019-10-17
• Study First Submitted QC: 2020-01-24
• Study First Posted: 2020-01-28
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-15
• Last Update Posted: 2020-04-16
• Study Start: 2020-08-15
• Primary Completion: 2020-08-15
• Study Completion: 2020-10-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 56

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cohort A	CHOP	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 A	R-CHOP	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	R-CHOP	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.
Cohort B	CHOP	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.
Cohort A	Vincristine Sulfate Liposome	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	Vincristine Sulfate Liposome	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.

Primary Outcome Measures

Name	Time	Method
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.