Hematologic Diseases
Conditions
Keywords
Hematology, Hematological Malignancy, CHOP, R-CHOP
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.
Interventions
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.
COMBINATION_PRODUCTCHOP
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)
COMBINATION_PRODUCTR-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)
Sponsors
Axis Clinicals Limited
Acrotech Biopharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Contacts
Primary ContactMelissa Brugard, CTM, MSW
Outcome results
None listed