Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Treatment of Elderly Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic (MD) Syndrome With Laromustine and Infusional Cytarabine

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Weill Medical College of Cornell University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Vion Pharmaceuticals
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00655395
First received: April 3, 2008
Last updated: March 8, 2010
Last verified: March 2010

April 3, 2008
March 8, 2010
March 2008
April 2010   (final data collection date for primary outcome measure)
The objectives of this study are to evaluate the safety and efficacy of VNP40101M in combination with infusional Ara C as induction therapy in elderly patients with AML or high-risk MDS evolving to AML. [ Time Frame: Subjects will be closely monitored continuously throughout the study. ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00655395 on ClinicalTrials.gov Archive Site
The secondary objective of this study is to evaluate this regimen for toxicities in this elderly population. [ Time Frame: Subjects will be closely monitored continuously throughout the study. ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Treatment of Elderly Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic (MD) Syndrome With Laromustine and Infusional Cytarabine
A Phase I/Phase II Evaluation of Laromustine (VNP40101M), A Sulfonylhydrazine Alkylating Agent, Combined With Infusional Cytarabine in Elderly Patients With Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome
  • The purpose of the Phase I portion of this study is to evaluate the safety of this combination of medications and to determine the appropriate dose of VNP40101M to be used in combination with infusional cytarabine (araC) in elderly patients with Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS).
  • The purpose of the Phase II portion of the study is to evaluate the effectiveness (overall response rate) for patients treated with VNP40101M and infusional cytarabine induction therapy.

There is no known standard chemotherapy that is considered effective for older patients with AML or high risk MDS at this time, and with current treatment, tumor reduction can be difficult to achieve and is short-lived. We are, therefore, interested in developing new drugs that might have a longer-lasting effect against disease.

Laromustine is a new drug that has been shown to have anti-cancer activity in animal and human studies. It interacts with the DNA of a cancer cell and kills the cell. Cytarabine (AraC) is a commercially available chemotherapy drug that is active against leukemia and used routinely when the disease is first diagnosed. In previous studies, when higher doses of laromustine were given, laromustine and AraC achieved more responses than patients treated with AraC alone. However, this advantage was offset by the fact that more patients given laromustine/AraC died to due side effects. We wish to determine the effectiveness of laromustine in combination with infusional AraC in AML and high risk MDS patients who are 60 or more years of age.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Myeloid Leukemia (AML)
  • Myelodysplastic Syndrome (MDS)
Drug: Laromustine (VNP40101M) and Ara-C
  1. Laromustine 300 mg/m2 (cohort 1), 400 mg/m2 (cohort 2), 500 mg/m2 (cohort 3) IV on day 1 over 30 - 60 minutes. Laromustine will be administered approximately 3-4 hours following the start of infusional Ara C.
  2. Ara C at 100 mg/m2/day as a continuous infusion daily for 7 days. Appropriate antiemetics are given during the Ara C infusion.
  • Experimental: 1
    1. Laromustine 300 mg/m2 (cohort 1) IV on day 1 over 30 - 60 minutes. Laromustine will be administered approximately 3-4 hours following the start of infusional Ara C.
    2. Ara C at 100 mg/m2/day as a continuous infusion daily for 7 days. Appropriate antiemetics are given during the Ara C infusion.
    Intervention: Drug: Laromustine (VNP40101M) and Ara-C
  • Experimental: 2
    1. Laromustine 400 mg/m2 (cohort 2) IV on day 1 over 30 - 60 minutes. Laromustine will be administered approximately 3-4 hours following the start of infusional Ara C.
    2. Ara C at 100 mg/m2/day as a continuous infusion daily for 7 days. Appropriate antiemetics are given during the Ara C infusion.
    Intervention: Drug: Laromustine (VNP40101M) and Ara-C
  • Experimental: 3
    1. Laromustine 500 mg/m2 (cohort 3) IV on day 1 over 30 - 60 minutes. Laromustine will be administered approximately 3-4 hours following the start of infusional Ara C.
    2. Ara C at 100 mg/m2/day as a continuous infusion daily for 7 days. Appropriate antiemetics are given during the Ara C infusion.
    Intervention: Drug: Laromustine (VNP40101M) and Ara-C
  • Experimental: 5
    1. Laromustine will be administered at the recommended phase II dose on day 1 over 30 - 60 minutes. Laromustine will be administered approximately 3-4 hours following the start of infusional Ara C.
    2. Ara C at 100 mg/m2/day as a continuous infusion daily for 7 days. Appropriate antiemetics are given during the Ara C infusion.
    Intervention: Drug: Laromustine (VNP40101M) and Ara-C
  • Experimental: 4
    1. Laromustine 600 mg/m2 (cohort 4) IV on day 1 over 30 - 60 minutes. Laromustine will be administered approximately 3-4 hours following the start of infusional Ara C.
    2. Ara C at 100 mg/m2/day as a continuous infusion daily for 7 days. Appropriate antiemetics are given during the Ara C infusion.
    Intervention: Drug: Laromustine (VNP40101M) and Ara-C
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
52
October 2010
April 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of AML based on WHO criteria (greater than 20% blasts in the bone marrow or blood) excluding AML M3, acute promyelocytic leukemia OR diagnosis of high-risk MDS defined as International Prognostic Scoring System INT-2.
  • ECOG performance status equal to 0, 1, 2.
  • No prior treatment for AML with myeloablative treatment. Patients may have prior treatment with a biologic therapy. Patients with MDS or AML that has evolved from MDS could have received prior low-dose cytotoxic therapy with agents such as azacytidine or low-dose Ara C.
  • Ability to sign an Informed Consent according to institutional guidelines.
  • Patients must have the following clinical laboratory values within 24 hours prior to beginning protocol treatment: a) serum creatinine less than or equal to 2.0mg/dl. b) total bilirubin less than or equal to 2.0 mg/dl c) ALT or AST less than or equal to 5 times the upper limit of normal.

Exclusion Criteria:

  • Uncontrolled active infection. Patients with infections who are under active treatment with antibiotics and whose infections are controlled may be entered into the study. Patients with chronic hepatitis are eligible.
  • Active heart disease including myocardial infarction, symptomatic coronary artery disease, arrhythmias not controlled by medication or uncontrolled congestive heart failure.
  • Severe pulmonary disease not controlled with medication.
  • Patients with serum creatinine > 2.0, serum bilirubin > 2.0. ALT or AST greater that 5 times the upper limit of normal. Patients with bilirubin or creatinine outside the acceptable levels will be considered eligible if this abnormality is clearly leukemia related and discussed with the principal's investigator prior to enrollment.
  • Patients concurrently receiving any other standard or investigational treatment for leukemia with the exception of hydroxyurea.
  • Since the formulation contains 30% ethanol, patients being treated with Antabuse (disulfiram) are excluded from the study.
  • Patients with APL t(15;17)
  • Patients with ECOG performance status of 3 or 4.
  • Patients should be off metronidazole (Flagyl) at least 24 hours before starting laromustine.
Both
60 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00655395
0702009008, VNP40101M
Not Provided
Ellen Ritchie, M.D. / Assistant Professor or Medicine, Weill Medical College of Cornell University
Weill Medical College of Cornell University
Vion Pharmaceuticals
Not Provided
Weill Medical College of Cornell University
March 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP