Prevention of Left Ventricular Dysfunction During Chemotherapy
Condition: Acute Myeloid Leukemia; Precursor-cell Lymphoblastic Leukemia-Lymphoma; Lymphoid Neoplasm; Multiple Myeloma; Lymphoma; Autologous Hematopoietic Stem Cell Transplantation
MeSH terms: Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Ventricular Dysfunction; Ventricular Dysfunction, Left
Study type: Interventional
Phase: Phase 3

Summary: 
      The investigators' objective is to assess the efficacy of the combined treatment with
      enalapril and carvedilol in the prevention of left ventricular systolic dysfunction in
      patients with hematological malignancies submitted to intensive chemotherapy with potential
      cardiotoxicity.

      The hypothesis is that these drugs administered during chemotherapy may prevent left
      ventricular systolic dysfunction.
    

Detailed description: 
      The prognosis of patients with hematological malignancies has greatly improved in the last
      years with the use of new chemotherapeutic drugs and regimens at the cost of significant
      adverse events such as cardiac toxicity. Asymptomatic left ventricular systolic dysfunction
      limits the specific treatment of the patients and their long-term survival, since a
      significant proportion of them will relapse within 5 years after front-line therapy and will
      require further salvage treatment, including hematopoietic stem-cell transplantation in most
      instances.

      Angiotensin-converting enzyme inhibitors (ACEIs) have showed to have preventive effects
      against chemotherapy-induced cardiotoxicity in animal models, and in patients with early
      cardiotoxicity. Carvedilol prevent free radical release, mitochondrial dysfunction,
      apoptosis, and dilated cardiomyopathy in animals treated with anthracyclines, and have shown
      promising results in preventing chemotherapy-induced left ventricular dysfunction in
      patients.

      As demonstrated in post-infarction patients, the combined treatment with an ACEI and
      carvedilol could have additive effects to prevent LV dysfunction in patients with
      hematological malignancies at high risk of cardiac toxicity. Therefore, we designed the
      OVERCOME (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in
      patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies)
      study, a prospective, randomized trial to evaluate the combined effect of enalapril and
      carvedilol on the prevention of left ventricular dysfunction in patients with malignant
      hemopathies undergoing intensive chemotherapy.
    

Intervention name(s): Enalapril and carvedilol
Intervention type(s): Drug
Intervention description(s): Enalapril 2.5 to 10 mg BID Carvedilol 6.25 to 25 mg BID
Intervention MeSH terms: Carvedilol; Enalapril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Prevention; ventricular dysfunction; chemotherapy; acute myeloid leukemia; precursor-cell lymphoblastic leukemia; multiple myeloma; lymphoma; ejection fraction; Autologous hematopoietic stem cell transplantation