Safety and Efficacy Study of AS101 to Treat Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by BioMAS Ltd
Sponsor:
Information provided by (Responsible Party):
BioMAS Ltd
ClinicalTrials.gov Identifier:
NCT01010373
First received: November 9, 2009
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Drug: AS101
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Application of AS101 in Combination With Chemotherapy for Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by BioMAS Ltd:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess safety and tolerability of AS101. [ Time Frame: Continously during study and maximum 6 months from the beginning of the study. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: January 2015
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AS101 infusions
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.
Drug: AS101
3 mg/m2 AS101 will be given intravenously (IV) three times per week.

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.

  Eligibility

Ages Eligible for Study:   60 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01010373

Contacts
Contact: Arnon Nagler, Prof +972-3-5305830 Arnon.Nagler@sheba.health.gov.il

Locations
Israel
Sheba Medical Center Not yet recruiting
Tel Hashomer, Israel
Contact: Arnon Nagler, Prof    03-5302588    Arnon.Nagler@sheba.health.gov.il   
Principal Investigator: Arnon Nagler, Prof         
Sponsors and Collaborators
BioMAS Ltd
  More Information

Additional Information:
No publications provided

Responsible Party: BioMAS Ltd
ClinicalTrials.gov Identifier: NCT01010373     History of Changes
Other Study ID Numbers: #77REV00
Study First Received: November 9, 2009
Last Updated: July 16, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by BioMAS Ltd:
Primary Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) induced AML.

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Ammonium trichloro(dioxoethylene-O,O'-)tellurate
Adjuvants, Immunologic
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014