Back to resultsSafety and Efficacy Study of AS101 to Treat Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Patients
Primary Purpose
Acute Myeloid Leukemia, Myelodysplastic Syndrome
Status
Suspended
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
AS101
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Primary Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) induced AML.
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of primary AML or AML transformed myelodysplastic syndrome (MDS) with FAB classification other than M3 as proven by bone marrow aspiration.
- Age ≥60 years.
- ECOG performance status of 0-2 (Karnofsky >60%).
- Adequate renal functions: Serum Creatinine < 2 times the upper limit of normal (ULN).
- Adequate hepatic function: serum AST and ALT ≤ 3 x ULN.
- Patients with reproductive potential must use an effective contraceptive method through the study. Patients must receive contraceptive and/or fertility counseling prior to entering the study, i.e., information on sperm banking, etc.
Exclusion Criteria:
- Patients receiving any other investigational agents.
- Symptomatic CNS involvement.
- History of pancreatitis or active alcohol abuse.
- Histologic diagnosis of FAB M3 AML.
- Life expectancy of less than 1 month.
- Patient receives Myelotarg (ozogamicin gemtuzumab).
- Use of hematopoietic growth factors such as G-CSF within 1 week prior to treatment initiation.
- Pregnant or lactating females.
- Patient has known human immunodeficiency virus (HIV) infection or known HIV-related malignancy; Patient has active hepatitis A, B or C infection.
- Active, uncontrolled, systemic infection considered opportunistic, life threatening, or of clinical significance at the time of treatment, or any severe concurrent disease which, in the opinion of the investigator, would make the patient inappropriate for trial entry.
- The patient has had congestive heart failure - New York Heart Association (CHF-NYHA) grade II or higher, and/or myocardial infarction within the last 12 months, or any cardiac disorder which, in the opinion of the Investigator, could put the patient at risk of clinically relevant arrhythmia.
Sites / Locations
- Sheba Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AS101 infusions
Arm Description
In addition to induction chemotherapy AS101 will be given intravenously. The patient will also receive AS101 infusions during the time break till the next chemotherapy course, as long as the patient does not achieve complete remission and the platelet count is <20,000/μl; ANC <1000. AS101 will be administered likewise up to two consolidation or equivalent chemotherapy courses (re-induction or salvage in the event that no CR is achieved following first induction chemotherapy), i.e., total of three chemotherapy courses.
Outcomes
Primary Outcome Measures
Time (days) to reach platelet counts ≥20,000/µl after first induction course and post-remission chemotherapy courses.
Secondary Outcome Measures
To assess safety and tolerability of AS101.
Reduction in bone marrow blasts from baseline throughout the study period.
Time (days) to reach platelets counts ≥50,000/µl after first induction course and subsequent post-remission chemotherapy courses.
Time (days) to reach platelets counts ≥100,000/µl after first induction course and subsequent post-remission chemotherapy courses.
Time (days) to reach the maximum platelets counts after chemotherapy courses throughout the study period.
To evaluate the number of platelet transfusions through the study period.
To measure the incidence and severity of bleeding events using the World Health Organization (WHO) Bleeding Scale, during the treatment and follow-up periods.
To assess a correlation between VLA-4 expressions level of leukemia blasts in vitro and the response to treatment in terms of blasts percent.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01010373
Brief Title
Safety and Efficacy Study of AS101 to Treat Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Patients
Official Title
Application of AS101 in Combination With Chemotherapy for Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Suspended
Why Stopped
The sponsor is currently focusing on different indications
Study Start Date
January 2015 (undefined)
Primary Completion Date
January 2016 (Anticipated)
Study Completion Date
January 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMAS Ltd
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether addition of AS101 to the standard chemotherapy regimen is effective in the treatment of newly diagnosed elderly (≥60) AML patients and AML transformed myelodysplastic syndrome (MDS) patients.
Detailed Description
AML patients frequently develop cytopenia, which can result in life-threatening bleeding and infections. Despite the administration of prophylactic platelet transfusions, these patients remain at risk of clinically significant hemorrhage. There is a growing need for new, innovative strategies, because the outcome for AML patients, particularly for the older ones, has not substantially changed in the last three decades. Thus, novel compounds to target the tumor cell's resistance to chemotherapeutic agents are essential for the improvement of patients' prognoses. AS101 is a non-toxic, organic, tellurium-based small compound with immunomodulating properties which have previously shown bone marrow sparing effect. In addition in preclinical studies AS101 has shown synergistic effect with several cytotoxic drugs. This study will investigate the safety and efficacy of AS101 formulation in combination with the standard therapy for newly diagnosed elderly AML and AML transformed MDS patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndrome
Keywords
Primary Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) induced AML.
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AS101 infusions
Arm Type
Experimental
Arm Description
In addition to induction chemotherapy AS101 will be given intravenously. The patient will also receive AS101 infusions during the time break till the next chemotherapy course, as long as the patient does not achieve complete remission and the platelet count is <20,000/μl; ANC <1000. AS101 will be administered likewise up to two consolidation or equivalent chemotherapy courses (re-induction or salvage in the event that no CR is achieved following first induction chemotherapy), i.e., total of three chemotherapy courses.
Intervention Type
Drug
Intervention Name(s)
AS101
Intervention Description
3 mg/m2 AS101 will be given intravenously (IV) three times per week.
Primary Outcome Measure Information:
Title
Time (days) to reach platelet counts ≥20,000/µl after first induction course and post-remission chemotherapy courses.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
Secondary Outcome Measure Information:
Title
To assess safety and tolerability of AS101.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
Title
Reduction in bone marrow blasts from baseline throughout the study period.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
Title
Time (days) to reach platelets counts ≥50,000/µl after first induction course and subsequent post-remission chemotherapy courses.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
Title
Time (days) to reach platelets counts ≥100,000/µl after first induction course and subsequent post-remission chemotherapy courses.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
Title
Time (days) to reach the maximum platelets counts after chemotherapy courses throughout the study period.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
Title
To evaluate the number of platelet transfusions through the study period.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
Title
To measure the incidence and severity of bleeding events using the World Health Organization (WHO) Bleeding Scale, during the treatment and follow-up periods.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
Title
To assess a correlation between VLA-4 expressions level of leukemia blasts in vitro and the response to treatment in terms of blasts percent.
Time Frame
Continously during study and maximum 6 months from the beginning of the study.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of primary AML or AML transformed myelodysplastic syndrome (MDS) with FAB classification other than M3 as proven by bone marrow aspiration.
Age ≥60 years.
ECOG performance status of 0-2 (Karnofsky >60%).
Adequate renal functions: Serum Creatinine < 2 times the upper limit of normal (ULN).
Adequate hepatic function: serum AST and ALT ≤ 3 x ULN.
Patients with reproductive potential must use an effective contraceptive method through the study. Patients must receive contraceptive and/or fertility counseling prior to entering the study, i.e., information on sperm banking, etc.
Exclusion Criteria:
Patients receiving any other investigational agents.
Symptomatic CNS involvement.
History of pancreatitis or active alcohol abuse.
Histologic diagnosis of FAB M3 AML.
Life expectancy of less than 1 month.
Patient receives Myelotarg (ozogamicin gemtuzumab).
Use of hematopoietic growth factors such as G-CSF within 1 week prior to treatment initiation.
Pregnant or lactating females.
Patient has known human immunodeficiency virus (HIV) infection or known HIV-related malignancy; Patient has active hepatitis A, B or C infection.
Active, uncontrolled, systemic infection considered opportunistic, life threatening, or of clinical significance at the time of treatment, or any severe concurrent disease which, in the opinion of the investigator, would make the patient inappropriate for trial entry.
The patient has had congestive heart failure - New York Heart Association (CHF-NYHA) grade II or higher, and/or myocardial infarction within the last 12 months, or any cardiac disorder which, in the opinion of the Investigator, could put the patient at risk of clinically relevant arrhythmia.
Facility Information:
Facility Name
Sheba Medical Center
City
Tel Hashomer
Country
Israel
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Study of AS101 to Treat Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Patients
We'll reach out to this number within 24 hrs