Recurrent Adult Acute Myeloid Leukemia Clinical Trial
Official title:
Phase 1/2 Study of Concurrent Decitabine in Combination With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults With Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS)
Verified date | January 2020 |
Source | Fred Hutchinson Cancer Research Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This phase I/II trial studies the side effects and best dose of decitabine when given together with filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly diagnosed, has come back or has not responded to treatment. Drugs used in chemotherapy, such as decitabine, cladribine, cytarabine, and mitoxantrone hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Colony-stimulating factors, such as filgrastim, may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Decitabine, filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride may work better in treating patients with acute myeloid leukemia and myelodysplastic syndrome.
Status | Completed |
Enrollment | 28 |
Est. completion date | October 24, 2018 |
Est. primary completion date | October 24, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - For patients with newly diagnosed disease: diagnosis of "high-grade" MDS (>= 10% blasts by morphology) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; for patients with relapsed/refractory disease: prior diagnosis of "high-risk" MDS or non-APL AML, with relapsed/refractory disease according to 2003 recommendations of the International Working Group, requiring first or subsequent salvage therapy; patients with mixed phenotype acute leukemia (MPAL) are eligible - Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines - Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) are eligible if relapse occurs provided symptoms of graft-versus host disease are well controlled with stable use of immunosuppressive agents - Treatment-related mortality (TRM) score =< 9.2 as calculated with simplified model - Should be off any active therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all grade 2-4 non-hematologic toxicities should have resolved - May have previously received monotherapy with demethylating agents for MDS or AML or treatment with a mitoxantrone- or cladribine-based regimen for MDS or AML, including G-CLAM, but not demethylating agent as priming for or in combination with chemotherapy - Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment - Bilirubin =< 2.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to registration) - Serum creatinine =< 2.0 mg/dL (assessed within 14 days prior to registration) - Left ventricular ejection fraction >= 45%, assessed within 3 months prior to registration, e.g. by multigated acquisition scan (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure; if the patient had anthracycline-based therapy since the most recent cardiac assessment, cardiac evaluation should be repeated if there is clinical or radiographic suspicion of cardiac dysfunction, or if the previous cardiac assessment was abnormal - Women of childbearing potential and men must agree to use adequate contraception - Ability to understand and willingness to sign a written consent Exclusion Criteria: - Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment - Concomitant illness associated with a likely survival of < 1 year - Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)]); patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24-48 hours - Known hypersensitivity to any study drug - Pregnancy or lactation - Patients may not be receiving any other investigational agents |
Country | Name | City | State |
---|---|---|---|
United States | Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Fred Hutchinson Cancer Research Center | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants Experiencing Dose Limiting Toxicities (DLTs) at the Maximum Tolerated Dose (MTD) for Decitabine When Given Together With G-CLAM Toxicities (DLTs) (Phase I) | Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. MTD is defined as the highest dose studied in which the incidence of DLT is < 33%. Each participant was monitored for DLTs in the first 20 days of treatment. DLTs monitored included any grade 3 non-hematologic toxicity lasting more than 48 hours that resulted in more than a 7 day delay of the subsequent treatment cycle (except for febrile neutropenia or infection) any grade 4 or greater non-hematologic toxicity (except febrile neutropenia and infection unless a direct consequence of a treatment-related toxicity, and except constitutional symptoms if they recovered to grade 2 or less within 14 days) lack of recovery of the absolute neutrophil count to 500/microliter or greater and lack of self-sustained platelet count of at least 50,000/microliter by treatment day +49 with no evidence of residual leukemia |
Up to 49 days | |
Secondary | Number of Participants With Minimal Residual Disease Negative (MRDneg) Complete Remission (Phase II) | Compared to historical controls of filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride (G-CLAM) alone. A Simon Minimax two-stage design will be used. | Up to 1 year | |
Secondary | Number of Participants Who Achieved Remission (Complete Remission [CR]/CR With Incomplete Peripheral Blood Count Recovery [CRi]) | Up to 1 year | ||
Secondary | Number of Participants With Overall Survival | Up to 1 year | ||
Secondary | Number of Participants With Relapse-free Survival | Up to 1 year | ||
Secondary | Number of Participants With Event-free Survival | Up to 1 year |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT01564277 -
Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies
|
Phase 2 | |
Completed |
NCT01527045 -
Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies
|
Phase 2 | |
Completed |
NCT02484391 -
CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Granulocytic Sarcoma
|
Phase 1 | |
Active, not recruiting |
NCT02204085 -
A Phase I/II Trial of the MUC1 Inhibitor, GO-203-2C in Patients With Relapsed or Refractory Acute Myeloid Leukemia
|
Phase 1/Phase 2 | |
Completed |
NCT01427881 -
Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies
|
Phase 2 | |
Completed |
NCT01233921 -
Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer
|
N/A | |
Completed |
NCT01093586 -
Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
|
Phase 2 | |
Terminated |
NCT00387426 -
Sunitinib in Treating Patients With Idiopathic Myelofibrosis
|
Phase 2 | |
Active, not recruiting |
NCT01056614 -
Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies
|
Phase 2 | |
Completed |
NCT00093418 -
S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia
|
Phase 2 | |
Completed |
NCT00070551 -
GTI-2040 and High-Dose Cytarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
|
Phase 1 | |
Completed |
NCT00078858 -
Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
|
Phase 1/Phase 2 | |
Terminated |
NCT00052598 -
Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant
|
Phase 1/Phase 2 | |
Completed |
NCT00052520 -
Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation
|
Phase 1/Phase 2 | |
Terminated |
NCT00049582 -
Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia
|
Phase 1 | |
Completed |
NCT01798901 -
AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia
|
Phase 1 | |
Terminated |
NCT01876953 -
Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia
|
Phase 1/Phase 2 | |
Completed |
NCT02070458 -
Ixazomib, Mitoxantrone Hydrochloride, Etoposide, and Intermediate-Dose Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia
|
Phase 1 | |
Completed |
NCT02583893 -
Biomarkers in Predicting Treatment Response to Sirolimus and Chemotherapy in Patients With High-Risk Acute Myeloid Leukemia
|
Phase 2 | |
Completed |
NCT01555268 -
Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia
|
Phase 1 |