Safety, Tolerability Study of SG2000 in the Treatment of Advanced Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia

Sponsor

Spirogen (Industry)

Overall Status

Terminated

CT.gov ID

NCT02034227

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Chronic Lymphocytic Leukemia	Drug: SG2000	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SG2000 - 15 µg/m2/day Cohort 1 - will commence at 15 µg/m2/day intravenous doses of SG2000 until Maximum Tolerated Dose is determined.	Drug: SG2000 intravenous doses given on Days 1, 2, and 3 of each 21-day cycle (1 to 6 cycles). Other Names: DNA minor groove binding agent
Experimental: SG2000 - 30 µg/m2/day Cohort 2 - will commence at 30 µg/m2/day intravenous doses of SG2000 until Maximum Tolerated Dose is determined.	Drug: SG2000 intravenous doses given on Days 1, 2, and 3 of each 21-day cycle (1 to 6 cycles). Other Names: DNA minor groove binding agent

Arm

Intervention/Treatment

Experimental: SG2000 - 15 µg/m2/day

Cohort 1 - will commence at 15 µg/m2/day intravenous doses of SG2000 until Maximum Tolerated Dose is determined.

Drug: SG2000

intravenous doses given on Days 1, 2, and 3 of each 21-day cycle (1 to 6 cycles).

Other Names:

DNA minor groove binding agent

Experimental: SG2000 - 30 µg/m2/day

Cohort 2 - will commence at 30 µg/m2/day intravenous doses of SG2000 until Maximum Tolerated Dose is determined.

Drug: SG2000

intravenous doses given on Days 1, 2, and 3 of each 21-day cycle (1 to 6 cycles).

Other Names:

DNA minor groove binding agent

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of SG2000. [From 1st dose of SG2000 given on days 1, 2 and 3, every 21-days, for six 21-day cycles (approximately 16 weeks).]
The Maximum Tolerated Dose (MTD) will be determined based on the assessment of the dose-limiting toxicity (DLT) during the DLT period; period is defined as the time from the first dose intravenous doses of SG2000 for 3 consecutive days every 21 days for 1 to 6 cycles until unacceptable toxicity, consent withdrawal, or another reason to discontinue therapy intervenes.

Secondary Outcome Measures

safety profile [day -1 to day- 21 for six 21-day cycles .]
Any subject who receives at least 1 dose of SG2000 will be evaluated for safety. Subjects will be monitored for adverse events (AEs) and will undergo safety assessments including full physical examination, vital sign assessment, Eastern Cooperative Oncology Group (ECOG) performance status assessment, and laboratory testing.
area under the concentration-time curve (AUC) [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.]
pharmacokinetic (PK) parameter, noncompartmental analysis will be performed to estimate the plasma pharmacokinetic (PK) parameters of SG2000. Area under the concentration-time curve (AUC).
Maximum plasma concentration (Cmax) [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.]
pharmacokinetic (PK) parameter -Cmax is the observed maximum plasma or serum concentration after administration
time to reach Cmax [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.]
pharmacokinetic (PK) parameter - time to reach Cmax.
terminal half life (T1/2), [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.]
pharmacokinetic parameter - terminal half life
hematology and serum chemistry [baseline, days 1,2,3,4,8,15, and 21 for six 21-day cycles.]
predictors of Vascular Leak Syndrome (VLS)
Physical examination [baseline, day-1 to day 21 for six 21-day cycles.]
predictors of Vascular Leak Syndrome (VLS)
Vital signs [baseline, day-1 to day-21 for six 21-day cycles.]
predictors of Vascular Leak Syndrome (VLS)
bone marrow aspirate [day-1 (predose), and day 8 of Cycles 1 and 3 , and day 1 of Cycles 2 and 4]
pulse oximetry [baseline, day-1 to day-21 for six 21-day cycles.]
monitoring for Vascular Leak Syndrome (VLS)
electrocardiogram [days 1, 8, 15, 21, and at Day 22 after the last cycle or early termination.]
bone marrow aspirate [day-1 (predose), and day- 8 of each 21-day cycle (cycles 1 and 3) and day -1 of cycles 2 and 4]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.