Leukemia
Conditions
Keywords
carfilzomib, acute myeloid leukemia, acute lymphoblastic leukemia, phase I
Brief summary
This study is to test escalating doses of carfilzomib in patients with relapsed acute myeloid and acute lymphoblastic leukemia.
Detailed description
Several published studies have demonstrated the in vitro anti-leukemic activity of carfilzomib in leukemia cell lines as well as in primary human acute myeloid and acute lymphoblastic leukemia cells. The anti-leukemic activity of carfilzomib was consistently more potent than that of bortezomib, particularly at doses ≥27mg/m2. Importantly, patients treated on the phase I and phase II carfilzomib trials have had low rates of treatment-associated neuropathy. Several large collaborative groups have current phase II clinical trials that incorporate bortezomib into the treatment regimens for acute myeloid or acute lymphoblastic leukemia. Thus, there is a strong rationale for a study of carfilzomib, a potentially more potent proteasome inhibitor with less toxicity, in patients with relapsed acute leukemias.
Interventions
DRUGCarfilzomib
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Disease Related * Relapsed acute myeloid leukemia or relapsed acute lymphoblastic leukemia. Patients with primary refractory AML or ALL (after standard induction chemotherapy) are also eligible if they have evidence of persistent disease documented by bone marrow biopsy done within 14 days of trial entry. * Subjects must have disease documented on bone marrow biopsy done within 14 days of starting cycle 1 Demographic * Males and females ≥ 18 years old. * Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2. Laboratory * Peripheral blast count must be ≤ 30,000 on the first day of study drug administration. Leukopheresis and hydrea are acceptable measures of leuko-reduction prior to beginning the study drug. * Adequate hepatic function with ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement. Serum bilirubin ≤ 2.0 x ULN. * Adequate renal function with calculated creatinine clearance of ≥ 15 mL/min (calculated using the Cockcroft and Gault formula) or measured creatinine clearance ≥ 15 mL/min from 24 hour urine collection. * Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing. Ethical / Other * Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed. * Women of childbearing age must have a negative serum pregnancy test within 7 days prior to initiating therapy and be willing to not become pregnant to by using effective contraception while undergoing treatment and for at least 3 months afterwards. * Men must be willing not to father a new child while receiving therapy. They must use an effective barrier method of contraception during the study and for 3 months following the last dose.
Exclusion criteria
Subjects meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) | End of cycle 1 | A hematologic adverse event will not be considered a dose-limiting toxicity. Tumor lysis syndrome is not a dose-limiting toxicity. |
Secondary
| Measure | Time frame |
|---|---|
| To determine the rate of morphologic complete remission (CR) | Every 2 months for 2 years after first dose of study drug |
| To determine the rates of cytogenetic complete remission (CRc) morphologic complete remission with incomplete count recovery (CRi), overall response rate (CR+ CRi), partial remission (PR), stable disease and hematologic improvement. | Every 2 months for 2 years after first dose of study drug |
| To determine the time to response, remission duration, progression-free survival, event-free survival and overall survival of patients treated with carfilzomib. | Every 2 months for 2 years after first dose of study drug |
| To determine the safety and tolerability of carfilzomib by evaluating the number of participants with adverse events as a measure of safety and tolerability. | 30 days after end of treatment |
| To prospectively collect serum and bone marrow specimens to determine biomarkers of response and correlative ex vivo studies of the anti-leukemic activity of carfilzomib. | Baseline, Day 28 of cycles 1, 2, 4, 6 & End of Study |
Countries
United States
Outcome results
None listed