None listed
Conditions
Brief summary
The investigational product in this trial is Cloretazine (VNP40101M). Cytosine Arabinoside (AraC) is a known treatment. Currently, there is no known standard chemotherapy that is considered effective for patients with AML in first relapse. With existing treatments, tumor reduction can be difficult to achieve and is short-lived. Vion Pharmaceuticals, Inc. is interested in developing new drugs that might have a better effect against the disease. Hence, there is a need for trials such as this. This is a double-blind, randomised, two-arm, phase 3, placebo-controlled trial. For every six patients randomized on to this trial, four patients will receive study drug and two patients will receive placebo. AraC will be given to one group of patients in combination with Cloretazine (VNP40101M) and the other group of patients will receive AraC with placebo. The main clinical hypothesis under study is that the patients on the experimental arm have a higher overall response rate (ORR) compared to patients on the control arm, i.e., the main objective is to see if the group of patients with the Cloretazine (VNP40101M) added, do better than the group who receive AraC alone. Patients with AML in first relapse will be invited to take part in this study.
Interventions
A double-blind placebo-controlled phase III randomised multi-center study with Cloretazine (VNP40101M) and Cytosine Arabinoside (AraC).
The total duration of the interventions is 3 days. This includes 3 days of AraC and one 30-60 minutes infusion of Cloretazine (VNP40101M) or placebo on Day 2 as described below:
Intervention Group:
• AraC is administered at a dose of 1.5 gm/m2/day on Days 1-3 as a continuous infusion over 24 hrs.
• Cloretazine (VNP40101M) at a dose of 600 mg/m2 is given on Da
A double-blind placebo-controlled phase III randomised multi-center study with Cloretazine (VNP40101M) and Cytosine Arabinoside (AraC). The total duration of the interventions is 3 days. This includes 3 days of AraC and one 30-60 minutes infusion of Cloretazine (VNP40101M) or placebo on Day 2 as described below: Intervention Group: • AraC is administered at a dose of 1.5 gm/m2/day on Days 1-3 as a continuous infusion over 24 hrs. • Cloretazine (VNP40101M) at a dose of 600 mg/m2 is given on Day 2 over 30-60 minutes in an infusion of 5% Dextrose Injection, USP (United States Pharmacopeia). Blinding: The pharmacist will be unblinded. The subject, therapist, assessor and data analyst will remain blinded. An interim analysis is planned after the first 210 accrued patients. Criteria for Re-Treatment and Consolidation: (Glossary: Complete Response or Remission (CR). Complete Response p (CRp) is defined as meeting all criteria for CR except recovery of platelet counts to >100,000 uL) Patients with evidence of clinical progression are not eligible to receive additional protocol treatment. Patients without evidence of clinical progression, who have not achieved at least a CRp, may receive a second induction cycle, no earlier than day 35 and no later than day 60. Patients who attain at least a CRp after the first or second induction cycle will be eligible for one cycle of consolidation. Consolidation should begin within 6 weeks after initial documentation of CR or CRp. Patients will receive Cloretazine (VNP40101M)/AraC or placebo/AraC according to their original assignment.
Sponsors
Vion Pharmaceuticals, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must have AML (any WHO classification excluding acute promyelocytic leukemia) in first relapse after a first CR (complete response) or CRp (meeting all criteria for CR except recovery of platelet counts to >100,000 uL) determined by bone marrow aspirates and/or biopsies that contain = 10% blasts. The duration of first CR or CRp must have been at least 3 months but less than 24 months, calculated from the day CR or CRp was documented following the initial induction regimen to the day leukemia relapse was confirmed by recurrence of blasts in peripheral blood, bone marrow histopathology and/or histological proven central nervous system (CNS) or extramedullary disease.
Exclusion criteria
Uncontrolled active infection of any kind. Presence of any other severe medical condition that may compromise the safety of treatment.
Outcome results
None listed