Treatment of Relapsed or Refractory Acute Myeloblastic Leukemia

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Second-line induction therapy with fludarabine, idarubicin, cytarabine,Granulocyte colony-stimulating factor (G-CSF) and plerixafor, in patients with relapsed or refractory Acute Myeloblastic Leukemia (AML) aged 65 or younger.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PETHEMA Foundation
• Treatments: Cytarabine; Fludarabine; Fludarabine phosphate; Idarubicin; JM 3100; Plerixafor

Criteria

Inclusion Criteria:

• Diagnosis of AML according to the WHO criteria

• Relapsed or refractory AML as defined below First relapse after standard treatment with duration of the first remission less than year

• Refractoriness to an induction cycle that includes cytarabine and anthracyclines

• Nonpromyelocytic leukemia (absence of t(15;17) or PML-RARα rearrangement and its variants)

• Peripheral blood blast cell count less than 50 x 109/L. Hydroxyurea and leukopheresis can be used to lower the blast count prior to beginning treatment

• Age ≤ 65 years and ≥ 18 years

• ECOG performance status of 0-2

• Provide signed written informed consent

• Be able to comply with study procedures and follow-up examinations

• Be nonfertile or agree to use birth control during the study through the end of last treatment visit

• Adequate renal and hepatic function as indicated by all of the following:

Total bilirubin <1.5 x Institutional Upper Limit of Normal (ULN); and AST and ALT <2.5 xULN; and Serum creatinine <1.0 mg/dL; if serum creatinine <1.0 mg/dL, then, the estimated glomerular filtration rate (GFR) must be <60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation - Minimal impairment of cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) >40% on multigated acquisition (MUGA) scan or radionuclide angiographic scan; or Left ventricular fractional shortening >22% on echocardiography exam;

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia (APL, French-American-British [FAB] classification M3 or WHO classification of APL with t(15;17)(q22;q12), (PML/RARalfa and variants)

• AML secondary to previous treatment for myelodysplastic syndrome (MDS)

• Peripheral blood blast cell count ≥ 50 x 109/L. Hydroxyurea and leukopheresis can be used to lower the blast count prior to beginning treatment

• Prior investigational treatment within 30 days prior to the first dose of study drug. If any investigational treatment has been received prior to this time point, drug related toxicities must have recovered to Grade 1 or less prior to first dose of study drug

• Prior hematopoietic stem cell transplant (HSCT) (previous autologous hematopoietic stem cell transplant is allowed)

• Investigational agent received within 5 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug

• Impaired renal and liver function as indicated by the following:

Total bilirubin > 1.5 x upper limit of normal (ULN) provided that this is not attributable to AML itself; or AST and ALT > 2.5 xULN provided that this is not attributable to AML itself; or Serum creatinine > 1.0 mg/dL provided that the estimated glomerular filtration rate (GFR) is ≤ 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation

• Impaired cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) < 40% on multigated acquisition (MUGA) scan or radionuclide angiographic scan; or Left ventricular fractional shortening < 22% on echocardiography exam;

• Poor overall condition ECOG 3-4

• Refusal to sign the informed consent

• Unable to comply with study procedures and follow-up examinations

• Psychiatric disorders that could interfere with consent, study participation or follow-up

• Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)

• Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions:

Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed

• Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)

• Prior positive test for the human immunodeficiency virus (HIV)

• History of hypersensitivity to any of the study drugs