Advanced Hematologic Malignancies
Conditions
Keywords
acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, chronic myeloid\ leukemia in blast phase
Brief summary
Chemotherapy resistance is a major cause of death in patients with advanced hematologic malignancies. The proposed novel mechanism of action, non-cross resistance with chemotherapeutic agents currently used in the clinic, and lack of CPI-613-related myelosuppression preclinically and clinically to date make CPI-613 a suitable candidate for phase I clinical trial in these patients. The current trial is one of several clinical trials of CPI-613. Other clinical trials that are conducted in patients with solid tumors have already been initiated. The primary objective of this study is to determine the safety and MTD of CPI-613 when administered 2x weekly for 3 consecutive weeks. The secondary objective is to determine the PKs of CPI-613 following IV administration and to observe the anti-tumor effects of CPI-613, if any occur.
Interventions
DRUGCPI-613
This is a Phase I open label trial using a 2-stage dose-escalation scheme (single-patient & traditional stages): Single-Patient Dose-Escalation Stage: In the single-patient stage, a single patient will be accrued per dose level. The starting dose will be 420 mg/m². Dose level will be escalated (by doubling the previous dose) if there is no toxicity or if the toxicity is grade 1 or less. If toxicity is \>Grade 1, the traditional dose-escalation stage will be triggered. Traditional Dose-Escalation: All dose escalations conducted in this Traditional Dose-Escalation stage will be escalated according to the modified Fibonacci Dose-Escalation scheme.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* histologically or cytologically documented relapsed and/or refractory hematologic malignancy * Karnofsky Performance Status (KPS) of \>70%. * Must be ≥18 years of age. * Expected survival \>1 month. * Women of child-bearing potential must use accepted contraceptive methods * No radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy within the 3 weeks prior to treatment with CPI-613.
Exclusion criteria
* Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity. * Patients with active central nervous system (CNS) or epidural tumor. * Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease). * Pregnant women, or women of child-bearing potential not using reliable means of contraception. * Lactating females because the potential of excretion of CPI-613 into breast milk. * Life expectancy less than 1 month. * Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the safety and MTD of CPI-613 when administered 2x weekly for 3 consecutive weeks. | 3 weeks |
Secondary
| Measure | Time frame |
|---|---|
| To determine PKs of CPI-613 following IV administration. | 3 weeks |
Countries
United States
Outcome results
None listed