Chronic Myelogenous Leukemia Clinical Trial
Official title:
Phase I Study to Evaluate the Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in Patients With Chronic Myelogenous Leukemia
The leukemic stem cells (LSCs) are cells that self- renew and give rise to leukemia.
Eradication of LSC is required for cure. In chronic myelogenous leukemia (CML) LSCs are not
eradicated by imatinib (Gleevec) alone. Recent discovery by Dr. Shaoguang Li at University
of Massachusetts indicates that the LSCs can be targeted by a new drug zileuton (Chen et al.
Nature Genetics 2009; 41:783-792). Zileuton (approved for asthma) will be tested in a
combination with Gleevec. This combination has not been used previously to treat leukemia.
This is a Phase I study. The goal of this research is to evaluate the safety of the standard
anti-cancer drug imatinib and experimental drug zileuton.
More than twenty two thousand people live with chronic myelogenous leukemia in the United
States and more than five thousand people are expected to be diagnosed this year. The
majority of patients with this disease are diagnosed in what is called the chronic phase.
The standard treatment for this phase of the disease is therapy with a medication called
imatinib. This treatment can diminish the amount of disease to very low levels that only
very sensitive and specialized techniques can measure; it does not, however, provide a cure.
Dr. Shaoguang Li and colleagues at University of Massachusetts have published a unique
discovery that the arachidonate 5-lipoxygenase (5-LO) gene (Alox5) is a critical regulator
for LSCs in BCR-ABL-induced CML (Chen Y et al. Loss of the Alox5 gene impairs leukemia stem
cells and prevents chronic myeloid leukemia. Nature Genetics 41:783-792, 2009). In the
absence of Alox5, BCR-ABL failed to induce CML in preclinical studies. While deficiency in
Alox5 had no effect on normal hematopoiesis, impairment of the LSCs function through
differentiation and cell division of CML LSCs was observed. This defect led to a depletion
of LSCs and a failure of CML development. Treatment with a 5-LO inhibitor (zileuton) also
impaired the function of LSCs and prolonged survival. These results demonstrate that a
specific target gene can be found in cancer stem cells and its inhibition can completely
inhibit the function of these stem cells. These findings provide an exciting opportunity to
develop the first anti-cancer stem cell therapy for treating CML.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05088356 -
Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft
|
Phase 1 | |
| Recruiting |
NCT04904588 -
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
|
Phase 2 | |
| Completed |
NCT02592447 -
Cognitive Behavioral Intervention for Targeted Therapy Fatigue (CBT-TTF) Intervention
|
N/A | |
| Withdrawn |
NCT04282174 -
CD34+ Enriched Transplants From HLA-Compatible Patients With Hematologic Malignancies
|
Phase 2 | |
| Terminated |
NCT01397734 -
Arsenic Trioxide and Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia (CML)
|
Phase 1 | |
| Completed |
NCT00975975 -
Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent Graft-Versus_Host Disease (GVHD) After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer
|
Phase 2 | |
| Withdrawn |
NCT01011998 -
A Study of Imatinib and Valproic Acid in Patients With Chronic Myelogenous Leukemia (CML)
|
Phase 2 | |
| Completed |
NCT00378534 -
Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants
|
Phase 2 | |
| Completed |
NCT00098033 -
Investigation of Clofarabine in Acute Leukemias
|
Phase 2 | |
| Terminated |
NCT00852709 -
Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias
|
Phase 1 | |
| Completed |
NCT02581007 -
Reduced Intensity Conditioning Transplant Using Haploidentical Donors
|
Phase 2 | |
| Terminated |
NCT03547154 -
Polyethylene Glycol Interferon Alfa-2b (PEG Intron) Versus Interferon Alfa-2b (INTRON^® A) in the Treatment of Newly Diagnosed Chronic Myelogenous Leukemia (CML) (C98026)
|
Phase 2/Phase 3 | |
| Terminated |
NCT02709083 -
Dasatinib or Nilotinib Followed by Imatinib in Patients With Newly Diagnosed, Chronic Phase Chronic Myeloid Leukemia
|
Phase 2 | |
| Terminated |
NCT02145039 -
Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases
|
N/A | |
| Terminated |
NCT02146846 -
Population Pharmacokinetics of Imatinib in CML Patients in Iran
|
N/A | |
| Active, not recruiting |
NCT01036009 -
A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies
|
Phase 2 | |
| Completed |
NCT00990587 -
Study Evaluating the Tolerance and Biologic Activity of Oral Ciclopirox Olamine in Patients With Relapsed or Refractory Hematologic Malignancy
|
Phase 1 | |
| Terminated |
NCT00594308 -
In-Vivo Activated T-Cell Depletion to Prevent GVHD
|
N/A | |
| Terminated |
NCT00500006 -
A Phase I Dose Escalation Combination Study in Patients With Chronic Myelogenous Leukemia (CML) and Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL)(0457-009)(TERMINATED)
|
Phase 1 | |
| Completed |
NCT00493181 -
Interleukin 11, Thrombocytopenia, Imatinib in Chronic Myelogenous Leukemia (CML) Patients
|
Phase 2 |