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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: SG2000


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of SG2000. | 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. | From 1st dose of SG2000 given on days 1, 2 and 3, every 21-days, for six 21-day cycles (approximately 16 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety profile | 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. | day -1 to day- 21 for six 21-day cycles . | 
| area under the concentration-time curve (AUC) | pharmacokinetic (PK) parameter, noncompartmental analysis will be performed to estimate the plasma pharmacokinetic (PK) parameters of SG2000. 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. | 
| Maximum plasma concentration (Cmax) | pharmacokinetic (PK) parameter -Cmax is the observed maximum plasma or serum concentration after administration | 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. | 
| time to reach Cmax | pharmacokinetic (PK) parameter - 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. | 
| terminal half life (T1/2), | pharmacokinetic parameter - terminal half life | 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. | 
| hematology and serum chemistry | predictors of Vascular Leak Syndrome (VLS) | baseline, days 1,2,3,4,8,15, and 21 for six 21-day cycles. | 
| Physical examination | predictors of Vascular Leak Syndrome (VLS) | baseline, day-1 to day 21 for six 21-day cycles. | 
| Vital signs | predictors of Vascular Leak Syndrome (VLS) | baseline, day-1 to day-21 for six 21-day cycles. | 
| bone marrow aspirate |  | day-1 (predose), and day 8 of Cycles 1 and 3 , and day 1 of Cycles 2 and 4 | 
| pulse oximetry | monitoring for Vascular Leak Syndrome (VLS) | baseline, day-1 to day-21 for six 21-day cycles. | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leukemia