Clinical trial NCT02034227: Safety, Tolerability Study of SG2000 in the Treatment of Advanced Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia
Official title: An Open-Label, Phase 1/Phase 2 Study to Evaluate the Safety, Tolerability, and Antitumor Activity of the DNA Minor Groove Binding Agent SG2000 in the Treatment of Advanced Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Chronic Lymphocytic Leukemia
Keywords: leukemia
Lead sponsor: Spirogen
Sponsor class: INDUSTRY
First posted: 2014-01-13
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the experimental drug, SG2000 is safe and tolerable in the treatment of participants with advanced chronic lymphocytic leukemia and acute myeloid leukemia whose standard treatment did not work, whose cancer came back or who are not candidates for other types of standard therapy.


Eligibility criteria: Inclusion Criteria:

* male or female greater than or equal to 18 years of age
* have one of the following disease states: Acute Myeloid Leukemia (AML) (age \<60 years) with relapsed/refractory disease; •Chronic Lymphocytic Leukemia (CLL) with relapsed disease following a fludarabine-based regimen or relapsed disease following an alkylator-based regimen
* are recovered from the acute adverse effects of prior therapies (excluding alopecia and Grade ≤2 neuropathy).
* have blast counts that can be controlled by the use of hydroxycarbamide (500 to 3000 mg daily).
* have adequate hepatic function and renal function
* have an estimated life expectancy of \>3 months
* female subject must have a negative serum pregnancy result within 7 days before the start of the study; Both men and women must agree to use a medically acceptable form of contraception throughout the treatment period and for 3 months after discontinuation of treatment

Exclusion Criteria:

* are eligible for any standard therapy known to be life prolonging or life saving
* have diagnosis of AML French-American-British (FAB) classification (FAB) M3 (acute promyelocytic leukemia (APL))
* are receiving concurrent chemotherapy, radiotherapy, immunotherapy, biological or hormonal treatment for cancer.
* have undergone anticancer therapy including chemotherapy (except for hydroxycarbamide at a maximum daily dose of 3000 mg), endocrine therapy, immunotherapy, or the use of other investigational agents within 4 weeks before study entry.
* prior radiation therapy with volume of bone marrow treated over 25%.
* use of immunosuppressive therapy, including systemic steroids within 7 days before the first dose of SG2000.
* hyperleukocytosis (blast counts \>30 000/mm3).
* history of allogeneic stem cell or solid organ transplantation.
* positive serology for human immunodeficiency virus (HIV), hepatitis B or hepatitis C or have HIV-AIDS, or active hepatitis B or C.
* history of other invasive malignancy within 3 years except for cervical carcinoma in situ, nonmelanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has been surgically cured.
* have any coexisting medical condition that will substantially increase the risk associated with the subject's participation in the study.
* have psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of necessary studies.
* have persistent Grade 2 or greater toxicities from any cause (except alopecia or peripheral neuropathy).
* are pregnant or breast-feeding.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of SG2000.
timeFrame: From 1st dose of SG2000 given on days 1, 2 and 3, every 21-days, for six 21-day cycles (approximately 16 weeks).
Secondary outcomes:
measure: safety profile
timeFrame: day -1 to day- 21 for six 21-day cycles .
measure: area under the concentration-time curve (AUC)
timeFrame: day-1 of each 21-day cycle (cycles 1 and 3) at the following time points: predose, 15 minutes (middle of infusion), 30 minutes(end of infusion), and at 10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours after the end of infusion.
measure: Maximum plasma concentration (Cmax)
timeFrame: day-1 of each 21-day cycle (cycles 1 and 3) at the following time points: predose, 15 minutes (middle of infusion), 30 minutes (end of infusion), and at 10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours after the end of infusion.
measure: time to reach Cmax
timeFrame: day-1 of each 21-day cycle (cycles 1 and 3) at the following time points: predose, 15 minutes (middle of infusion), 30 minutes (end of infusion), and at 10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours after the end of infusion.
measure: terminal half life (T1/2),
timeFrame: day-1 of each 21-day cycle (cycles 1 and 3) at the following time points: predose, 15 minutes (middle of infusion), 30 minutes (end of infusion), and at 10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours after the end of infusion.
measure: hematology and serum chemistry
timeFrame: baseline, days 1,2,3,4,8,15, and 21 for six 21-day cycles.
measure: Physical examination
timeFrame: baseline, day-1 to day 21 for six 21-day cycles.
measure: Vital signs
timeFrame: baseline, day-1 to day-21 for six 21-day cycles.
measure: bone marrow aspirate
timeFrame: day-1 (predose), and day 8 of Cycles 1 and 3 , and day 1 of Cycles 2 and 4
measure: pulse oximetry
timeFrame: baseline, day-1 to day-21 for six 21-day cycles.
measure: electrocardiogram
timeFrame: days 1, 8, 15, 21, and at Day 22 after the last cycle or early termination.
measure: bone marrow aspirate
timeFrame: day-1 (predose), and day- 8 of each 21-day cycle (cycles 1 and 3) and day -1 of cycles 2 and 4
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
References: