Leukemia Clinical Trial
Official title:
A Phase I-II Study Evaluating the Safety and Efficacy of Imatinib Mesylate (Gleevec) Combined With Reinduction Chemotherapy Using Mitoxantrone, Etoposide and Cytarabine in Patients With Relapsed/Refractory C-kit Positive Acute Myeloid Leukemia
This is a Phase I-II study evaluating the toxicity and efficacy of imatinib combined with mitoxantrone, etoposide and high-dose cytarabine reinduction therapy in relapsed and refractory AML. Patients will be treated initially at a 200 mg dose of imatinib; if tolerated, the imatinib dose will be escalated in subsequent cohorts to 300 mg and 400 mg. Once the recommended dose is determined, the remaining patients will be treated at that dose, to evaluate the antileukemic activity of the regimen. Patients achieving complete remission will receive consolidation therapy with imatinib combined with high-dose cytarabine and mitoxantrone, followed by maintenance imatinib.
Status | Completed |
Enrollment | 35 |
Est. completion date | April 2010 |
Est. primary completion date | September 2009 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria: - AML, all subtypes except APL. - Prior induction therapy consisting of cytarabine 100-200 mg/m2 plus an anthracycline. - One of the following: - persistent leukemia after induction therapy. - relapse within two years of achieving complete remission with induction therapy. Any consolidation therapy is acceptable, including stem cell transplantation. - At least 10% bone marrow blasts, or biopsy confirmed extramedullary disease. - Positivity for c-kit (CD117) in at least 30% of blasts as measured by flow cytometry. - Aged 18-65. - ECOG performance status < 3 (see Appendix I). - No chemotherapy within the previous four weeks, other than hydroxyurea to control counts. If hydroxyurea is used, it must be stopped at least 24 hours prior to starting imatinib. - Able to given informed consent. Exclusion Criteria: - Active uncontrolled infection. - Active CNS leukemia. - Serum creatinine > 200 umol/L. - Serum bilirubin > 1.5 x ULN, AST or ALT > 2x ULN. - Left ventricular ejection fraction < 50%. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Canada | Princess Margaret Hospital | Toronto | Ontario |
Lead Sponsor | Collaborator |
---|---|
University Health Network, Toronto |
Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Toxicity (hematologic and non-hematologic) of the combination of Imatinib and Chemotherapy consisting of Mitoxantrone, Etoposide and Ara-c | Hematologic toxicity Number of days to ANC > 0.5 and 1.0. Number of days until platelets > 20 and > 50, independent of platelet transfusions. Number of days until RBC transfusion independent. Non-hematologic toxicity, as per NCI common toxicity criteria Hematologic dose-limiting toxicity (DLT) defined as > 40 days to ANC > 0.5 or platelets > 20 independent of transfusions. |
2 years | Yes |
Primary | Response rate - CR, MLFS and PR as per section 7.1 | Complete response Morphologic leukemia-free state Partial remission (PR•No response (NR): Does not meet the criteria for CR, MLFS or PR. |
2 years | Yes |
Primary | Maximum tolerated dose of Imatinib when given in combination with chemotherapy | Maximum tolerated dose (MTD) of Imatinib (200, 300, 400 mg) when used in combination with NOVE-HiDAC induction and consolidation. MTD defined as highest dose resulting in up to 2/6 grade III-IV hematologic (as defined above) or non-hematologic DLTs per dose level. Non-hematologic DLTs as defined by NCIC CTC. | 2 years | Yes |
Secondary | Toxicity of imatinib maintenance therapy. | Hematologic Number of days to ANC > 0.5 and 1.0. Number of days until platelets > 20 and > 50, independent of platelet transfusions. Number of days until RBC transfusion independent. Non-hematologic toxicity, as per NCI common toxicity criteria |
2 years | Yes |
Secondary | Number of Participants with adverse events as a measure of safety and tolerability | Toxicity of imatinib maintenance therapy. | 2 years | Yes |
Secondary | Remission-free survival and overall survival. | Median duration of remission free survival. Median overall survival and 2 year overall survival. | 2 years | Yes |
Secondary | Total and phosphorylated c-kit activity at Days 1 and 4. | levels of total and phosphorylated c-kit - pre and post imatinib/Gleevec | 2 years | No |
Secondary | Levels of downstream components of c-kit pathway at Days 1 & 4. | levels of phosphorylation ERK and AKT - pre and post imatinib/Gleevec | 2 years | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05691608 -
MoleculAr Profiling for Pediatric and Young Adult Cancer Treatment Stratification 2
|
N/A | |
Recruiting |
NCT04092803 -
Virtual Reality as a Distraction Technique for Performing Lumbar Punctures in Children and Young Adu
|
N/A | |
Active, not recruiting |
NCT02530463 -
Nivolumab and/or Ipilimumab With or Without Azacitidine in Treating Patients With Myelodysplastic Syndrome
|
Phase 2 | |
Completed |
NCT00948064 -
Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)
|
Phase 2 | |
Completed |
NCT04474678 -
Quality Improvement Project - "My Logbook! - I Know my Way Around!"; ("Mein Logbuch - Ich Kenne Mich Aus!")
|
N/A | |
Terminated |
NCT00801931 -
Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders
|
Phase 1/Phase 2 | |
Recruiting |
NCT03948529 -
RevErsing Poor GrAft Function With eLtrombopag After allogeneIc Hematopoietic Cell trAnsplantation
|
Phase 2 | |
Completed |
NCT01682226 -
Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies
|
Phase 2 | |
Completed |
NCT00003270 -
Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer
|
Phase 2 | |
Active, not recruiting |
NCT02723994 -
A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
|
Phase 2 | |
Terminated |
NCT02469415 -
Pacritinib for Patients With Lower-Risk Myelodysplastic Syndromes (MDS)
|
Phase 2 | |
Recruiting |
NCT04856215 -
90Y-labelled Anti-CD66 ab in Childhood High Risk Leukaemia
|
Phase 2 | |
Recruiting |
NCT06155188 -
Post-transplant PT/FLU+CY Promotes Unrelated Cord Blood Engraftment in Haplo-cord Setting in Childhood Leukemia
|
N/A | |
Completed |
NCT00001637 -
Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults
|
Phase 2 | |
Active, not recruiting |
NCT04188678 -
Resiliency in Older Adults Undergoing Bone Marrow Transplant
|
N/A | |
Completed |
NCT02910583 -
Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL)
|
Phase 2 | |
Completed |
NCT01212926 -
Early Detection of Anthracycline Cardiotoxicity by Echocardiographic Analysis of Myocardial Deformation in 2D Strain
|
N/A | |
Terminated |
NCT00014560 -
Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
|
Phase 1 | |
Recruiting |
NCT04977024 -
SARS-CoV-2 Vaccine (GEO-CM04S1) Versus mRNA SARS-COV-2 Vaccine in Patients With Blood Cancer
|
Phase 2 | |
Recruiting |
NCT05866887 -
Insomnia Prevention in Children With Acute Lymphoblastic Leukemia
|
N/A |