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

Phase 1
Terminated
Conditions
Acute Myeloid Leukemia
Chronic Lymphocytic Leukemia
Interventions
Registration Number
NCT02034227
Lead Sponsor
Spirogen
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SG2000 - 15 µg/m2/daySG2000Cohort 1 - will commence at 15 µg/m2/day intravenous doses of SG2000 until Maximum Tolerated Dose is determined.
SG2000 - 30 µg/m2/daySG2000Cohort 2 - will commence at 30 µg/m2/day intravenous doses of SG2000 until Maximum Tolerated Dose is determined.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
time to reach Cmaxday-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.

hematology and serum chemistrybaseline, days 1,2,3,4,8,15, and 21 for six 21-day cycles.

predictors of Vascular Leak Syndrome (VLS)

bone marrow aspirateday-1 (predose), and day- 8 of each 21-day cycle (cycles 1 and 3) and day -1 of cycles 2 and 4
pulse oximetrybaseline, day-1 to day-21 for six 21-day cycles.

monitoring for Vascular Leak Syndrome (VLS)

electrocardiogramdays 1, 8, 15, 21, and at Day 22 after the last cycle or early termination.
safety profileday -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.

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

Physical examinationbaseline, day-1 to day 21 for six 21-day cycles.

predictors of Vascular Leak Syndrome (VLS)

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

Vital signsbaseline, day-1 to day-21 for six 21-day cycles.

predictors of Vascular Leak Syndrome (VLS)

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).

Trial Locations

Locations (2)

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Duke University

🇺🇸

Durham, North Carolina, United States

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