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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: SG2000

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Spirogen

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: January 6, 2014
• First Submitted That Met QC Criteria: January 9, 2014
• First Posted (Estimate): January 13, 2014

Study Record Updates

• Last Update Posted (Estimate): November 23, 2015
• Last Update Submitted That Met QC Criteria: November 19, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: CL-2000-II-01