Phase 1, Dose Escalation Study To Assess the Safety, Pharmacokinetics and Activity of 2-Hour Continuous Intravenous Dosing of ON 013105 Administered Weekly in Patients With Relapsed/Refractory Lymphoma and Acute Lymphoid Leukemia
This is an open-label, dose-escalation Phase I study of ON 013105 in patients with
relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome
negative) who have satisfied all inclusion/exclusion criteria. Patients will receive weekly
2-hour IV infusions of ON 013105, until evidence of disease progression, intolerable adverse
events, or withdrawal of patient consent. Up to 12 additional patients will be treated at
the RPTD level. The starting dose will be 17 mg over a 2-hour weekly infusion. Each cycle
will comprise three weeks.
Up to 43 patients may be enrolled, of which approximately 7 to 37 patients will be enrolled
in the dose escalation portion of the study to determine the RPTD. After the maximally
administered dose is attained and at least six patients have received a tentative RPTD, up
to 6 additional patients may be enrolled in the dose confirmation phase to confirm the RPTD
Treatment will be administered in the Clinical Research center for the first dose for all
patients at each given dose level. If there is no toxicity, then subsequent doses at that
level for that patient may be administered on an outpatient basis, unless hospitalization is
required for another reason.
According to the Simon accelerated titration design, one-patient cohorts and 100% dose
increments will be implemented until non-hematological grade 2 toxicity is observed during
the first 3-week cycle. The design will then convert to standard 3/6 patient cohorts
starting at the dose level where grade 2 toxicity was observed and following 40% dose
increments for the subsequent cohorts.
If none of the first three patients experiences a dose-limiting toxicity (DLT) during the
first cycle (3 weeks), the next 3 patients will receive the next dose level. If there is a
DLT in one of the first three patients, this dose level will be expanded to 6 patients. If 1
patient out of 6 experiences DLT, the next patients will receive the next dose level. If ≥ 2
patients experience DLT at any dose level, this dose level will be declared the Maximally
Administered Dose. The Maximally Tolerated Dose (MTD) and RPTD will be the highest dose
level below the Maximally Administered Dose with 0 out of 3 patients or one out of 6
patients with DLT. Dosing will be reduced to the immediate lower dose for any patient who
experiences a DLT at any time.
If Grade 1 non-hematological toxicity occurs, treatment will be continued at the original
dose without dose reduction.
Patients with stable disease or response can continue treatment up to eight 3-week cycles.
Further continuation will be determined by the clinical judgment of the Investigator.
Patients who drop out for any reason may not re-enter the trial.
Blood samples will be collected during Day 1 of the first cycle for pharmacokinetic
assessment. Responses will be assessed according to Cheson, B.D., et al., Revised Response
Criteria for Malignant Lymphoma, J Clin Oncol 2007. 25: p. 579-86.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety based on adverse events, hematology and chemical laboratory values, urinalysis, coagulation, ECG, vital signs, physical examination.
Jennifer Cultrera, MD
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center & Research Institute||Tampa, Florida 33612|