Acute Lymphoblastic Leukemia
Conditions
Brief summary
The purpose of this study is to find the highest safe dose and to assess the anti-tumor effect of liposomal vincristine with dexamethasone in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose (MTD) of liposomal vincristine given with dexamethasone in patients with relapsed or refractory acute lymphoblastic leukemia (ALL). * Determine the efficacy of liposomal vincristine given with dexamethasone in these patients.
Interventions
Study treatment consists of infusion of VSLI intravenously over 60 minutes on Day 1 and Days 8, 15 and 22 (+/- 2 days).
DRUGDexamethasone
Study treatment consists of 40 mg dexamethasone, daily orally or intravenously, on Days 1-4 (+/- 2 days) and Days 11-14 (+/- 2 days).
Sponsors
Acrotech Biopharma Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Previously treated, relapsed or refractory ALL (including lymphoblastic lymphoma and Burkitt's subtypes) with measurable disease. * Performance status ≤3 (ECOG). * All ages are eligible. Those aged 12 years or older may be counted towards the MTD in the Phase I portion of the trial. Pediatric patients are eligible, but must be treated at a dose level previously tested in an adult (one full course). * Adequate liver function (bilirubin ≤2 x upper limit normal), and renal function (creatinine ≤2 x upper limit normal). * Negative pregnancy test in females of childbearing potential. * Patients with prior history of stem cell transplant are eligible if they meet all other eligibility requirements.
Exclusion criteria
* Active serious infection not controlled by oral or intravenous antibiotics. * Treatment with any investigational agents or chemotherapy agents in the last 21 days before study entry, unless full recovery from side effects has occurred or the patient has rapidly progressive disease judged to be life threatening by the Investigator. * Concurrent treatment with other anti-cancer agents other than dexamethasone. * Known CNS leukemia or lymphoma requiring intrathecal or craniospinal radiation therapy or with CNS neuropathy limiting evaluation of study drug. Patients with controlled CNS disease (no progression signs or symptoms at the time of study entry) may be eligible after approval by the Principal Investigator. Lumbar puncture not required in asymptomatic patients. * Prior history of Grade 3 or 4 sensory or motor neuropathy related to chemotherapeutic treatment, or persistent Grade 2 or greater active neuropathy. * History of active neurologic disorders unrelated to chemotherapy (including familial neurologic diseases and acquired demyelinating disorders). * Prior history of hypersensitivity reactions to vincristine or any of the other components of VSLI. * Pregnant and/or lactating women; or fertile men or women not willing to use contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD of VSLI | 6 weeks | Subjects had to receive at least 1 course consisting of 4 weekly infusions of VSLI at the assigned drug dose with a minimum 2 weeks of observation after the last VSLI dose to be included in the evaluation of the MTD. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VSLI Vincristine Sulfate Liposomes Injection (VSLI) | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | VSLI |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants |
| Age, Continuous | 36.3 years STANDARD_DEVIATION 13.83 |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 36 |
| serious Total, serious adverse events | 33 / 36 |
Outcome results
Primary
MTD of VSLI
Subjects had to receive at least 1 course consisting of 4 weekly infusions of VSLI at the assigned drug dose with a minimum 2 weeks of observation after the last VSLI dose to be included in the evaluation of the MTD.
Time frame: 6 weeks
Population: This study was designed to define the MTD of VSLI. Up to 7 sequential escalating dose cohorts (1.5, 1.825, 2.0, 2.25, 2.4, 2.6, and 2.8 mg/m2) were planned, with at least 3 subjects in each cohort. Escalation to the next higher dose cohort was allowed to proceed only if no nonhematologic DLT was observed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VSLI | MTD of VSLI | 2.25 mg/m2 |