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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Spirogen
Sponsor:
Information provided by (Responsible Party):
Spirogen
ClinicalTrials.gov Identifier:
NCT02034227
First received: January 6, 2014
Last updated: January 9, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Acute Myeloid Leukemia
Chronic Lymphocytic Leukemia
Drug: SG2000
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Spirogen:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of SG2000. [ Time Frame: From 1st dose of SG2000 given on days 1, 2 and 3, every 21-days, for six 21-day cycles (approximately 16 weeks). ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: day -1 to day- 21 for six 21-day cycles . ] [ Designated as safety issue: No ]

    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) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    pharmacokinetic (PK) parameter -Cmax is the observed maximum plasma or serum concentration after administration

  • time to reach Cmax [ Time Frame: 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. ] [ Designated as safety issue: No ]
    pharmacokinetic (PK) parameter - time to reach Cmax.

  • terminal half life (T1/2), [ Time Frame: 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. ] [ Designated as safety issue: No ]
    pharmacokinetic parameter - terminal half life

  • hematology and serum chemistry [ Time Frame: baseline, days 1,2,3,4,8,15, and 21 for six 21-day cycles. ] [ Designated as safety issue: No ]
    predictors of Vascular Leak Syndrome (VLS)

  • Physical examination [ Time Frame: baseline, day-1 to day 21 for six 21-day cycles. ] [ Designated as safety issue: No ]
    predictors of Vascular Leak Syndrome (VLS)

  • Vital signs [ Time Frame: baseline, day-1 to day-21 for six 21-day cycles. ] [ Designated as safety issue: No ]
    predictors of Vascular Leak Syndrome (VLS)

  • bone marrow aspirate [ Time Frame: day-1 (predose), and day 8 of Cycles 1 and 3 , and day 1 of Cycles 2 and 4 ] [ Designated as safety issue: No ]
  • pulse oximetry [ Time Frame: baseline, day-1 to day-21 for six 21-day cycles. ] [ Designated as safety issue: No ]
    monitoring for Vascular Leak Syndrome (VLS)

  • electrocardiogram [ Time Frame: days 1, 8, 15, 21, and at Day 22 after the last cycle or early termination. ] [ Designated as safety issue: No ]
  • bone marrow aspirate [ Time Frame: day-1 (predose), and day- 8 of each 21-day cycle (cycles 1 and 3) and day -1 of cycles 2 and 4 ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: April 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: DNA minor groove binding agent

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02034227

Contacts
Contact: John Barnes, Senior Global Project Manager 512-484-9502 john.barnes@ppdi.com
Contact: Matthew Cramblett, AD, Hematology/ +44 1698 572928

Locations
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27705
Contact: David Rizzieri, MD         
Principal Investigator: David Rizzieri, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Robert Stuart, MD         
Principal Investigator: Robert Stuart, MD         
Sponsors and Collaborators
Spirogen
  More Information

No publications provided

Responsible Party: Spirogen
ClinicalTrials.gov Identifier: NCT02034227     History of Changes
Other Study ID Numbers: CL-2000-II-01
Study First Received: January 6, 2014
Last Updated: January 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Spirogen:
leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 26, 2014