Acute Myelogenous Leukemia Clinical Trial
Official title:
A Phase I Study Using Bortezomib (Velcade, Formerly Known as PS-341) With Weekly Idarubicin for the Treatment of Elderly (>/= 60 Years) and Relapsed Patients With Acute Myelogenous Leukemia
The purpose of this study is to determine the maximal tolerated dose (MTD) of bortezomib and
idarubicin given in combination to newly diagnosed AML patients >60 years or relapsed AML
patients.
Another purpose of this study is to determine the dose limiting toxicities associated with
bortezomib in combination with idarubicin in newly diagnosed AML patients >60 years or
relapsed AML patients.
Status | Completed |
Enrollment | 55 |
Est. completion date | October 2008 |
Est. primary completion date | October 2008 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Age: > 60 years of age for newly diagnosed/transformed disease; > 18 years of age for relapsed disease. - AML with or without antecedent hematologic disorder diagnosed by morphologic, histochemical, or cell surface marker criteria - as defined by the WHO classification (17). - Newly diagnosed, elderly patients who are considered unsuitable for intensive chemotherapy induction -- antecedent hematologic disorders, pre-existing myelodysplasia, trilineage dyspoiesis, unfavorable cytogenetics, or pre-existing comorbidities. - Untreated conditions meeting criteria the first and third criteria or patients with diagnosis as in criteria 2 who have relapsed after at least one successful induction therapy. (Relapsed patients treated on this protocol will be patients without a suitable donor for transplant or for whom transplant is not an option for other reasons.) - Karnofsky performance status >60. - Adequate cardiac function as evidenced by an ejection fraction on MUGA >/= 40, as well as no evidence of uncontrolled hypertension, New York Heart Class III/IV congestive heart failure, angina pectoris, or ventricular dysrhythmias. - Adequate renal function as evidenced by a calculated creatinine clearance >/= 30ml/min (Cockcroft-Gault formula). - Adequate pulmonary function as evidenced by room air and exercise saturations >/= 92 or DLCO >/= 40% or FEV1 >/= 60% of predicted. - Adequate liver function as evidenced by SGOT/SGPT less than 5 times the ULN and total Bilirubin less than 2 times the ULN except where abnormalities are directly attributable to leukemia. - Adequate neurologic function -- patients must be currently free of active CNS leukemia as evidenced by cytospin of CSF from lumbar puncture if there is any clinical suspicion for CNS leukemia. As well, patients must not have >/= grade 2 neuropathy by NCI common toxicity criteria (CTC), Version 3.0. - Prior anthracycline dose in relapsed patients must not exceed 72 mg/m^2 of idarubicin or any dose equivalent to 300 mg/m^2 of adriamycin. - Patients must be informed and sign a written consent. Exclusion Criteria: - Patients with acute promyelocytic leukemia. Patients with uncontrolled systemic infection. - Patients who are known to be HIV seropositive. - Patients with evidence of CNS leukemia. - Patients who are pregnant or lactating. - Patients with primarily refractory disease unresponsive to a standard induction regimen. - Patients with a new diagnosis as per inclusion criteria 2, but for whom standard induction chemotherapy would be expected to be well tolerated and a preferred option in the opinion of the principal investigator. - Patients with relapsed AML, but for whom a suitable donor of stem cells exists and in whom high-dose chemotherapy with hematopoietic stem cell transplant is felt to be a better immediate alternative. - Patients with any clinically significant abnormality in screening blood chemistry, hematology or urinalysis results that, in the judgment of the investigator, would impede adequate evaluation of adverse events and/or response to treatment, or that requires aggressive intervention. - Patients with hypersensitivity to Bortezomib, boron, or mannitol. |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | University of Kentucky | Lexington | Kentucky |
United States | University of Rochester | Rochester | New York |
Lead Sponsor | Collaborator |
---|---|
University of Kentucky | National Institutes of Health (NIH) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum tolerated dose of bortezomib & idarubicin given in combination, with idarubicin given once weekly for 4 consecutive weeks & bortezomib given twice weekly over the same time. | week 4 | Yes | |
Primary | Dose limiting toxicities associated with bortezomib in combination with idarubicin. | week 4 | Yes | |
Secondary | Response to the combination of Idarubicin and Bortezomib. | Days 18 & 50 | No | |
Secondary | Pre- & post-treatment inhibition of NF-kB activity in the malignant & normal hematopoietic cell populations. | 24 hours after the initial dose of Bortezomib | No | |
Secondary | Induction of p53 levels in the malignant cell populations. | 2 and 24 hours post day +1 Bortezomib | No | |
Secondary | Bortezomib PK when administered to patients with acute leukemia receiving concomitant medications that could lead to drug interactions. In the case of altered pharmacokinetics, a pharmacodynamic assay to check proteasome inhibition may also be applied. | Days 1, 4, 8, 11, 15 | No | |
Secondary | Idarubicin PK in order to observe any alteration in metabolism/elimination of Idarubicin & its active metabolite idarubicinol when it is combined with Bortezomib. | Days 1, 4, 8, 11, 15 | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01200355 -
Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
|
Phase 4 | |
Active, not recruiting |
NCT03755414 -
Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation
|
Phase 1 | |
Recruiting |
NCT04904588 -
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
|
Phase 2 | |
Active, not recruiting |
NCT04188678 -
Resiliency in Older Adults Undergoing Bone Marrow Transplant
|
N/A | |
Completed |
NCT02543879 -
Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies
|
Phase 1 | |
Completed |
NCT01681537 -
Lenalidomide Plus Chemotherapy for AML
|
Phase 1 | |
Completed |
NCT01385423 -
Haploidentical Donor Natural Killer Cell Infusion With IL-15 in Acute Myelogenous Leukemia (AML)
|
Phase 1 | |
Terminated |
NCT01193400 -
Clofarabine and Low-dose Cytarabine Followed by Consolidation Therapy in AML Patients Age Greater Than or Equal to 60 Years
|
Phase 2 | |
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 | |
Completed |
NCT00995332 -
Disease Stabilization in AML by Treatment With ATRA, Valproic Acid and Low-dose Cytarabine
|
Phase 1/Phase 2 | |
Completed |
NCT00981240 -
Dose Escalation, Safety and Pharmacokinetic Study of SAR103168 in Patients Refractory/ Relapsed Acute Leukemias or High-risk Myelodysplastic Syndromes
|
Phase 1 | |
Completed |
NCT00726934 -
The Effectiveness of the Neutropenic Diet in Pediatric Oncology Patients
|
N/A | |
Completed |
NCT00378534 -
Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants
|
Phase 2 | |
Completed |
NCT01031498 -
Palonosetron Versus Ondansetron for the Prevention of Nausea and Vomiting
|
Phase 2 | |
Completed |
NCT00789256 -
Low Dose Melphalan and Bortezomib for AML and High-Risk MDS
|
N/A | |
Completed |
NCT00098033 -
Investigation of Clofarabine in Acute Leukemias
|
Phase 2 | |
Completed |
NCT01020539 -
Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia
|
Phase 1 | |
Not yet recruiting |
NCT04709458 -
Safety and Early Efficacy Study of TBX-2400 in Patients With AML or Myelofibrosis
|
Phase 1 | |
Recruiting |
NCT04024241 -
Medium Dose of Cytarabine and Mitoxantrone
|
||
Terminated |
NCT02203773 -
Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)
|
Phase 1 |