Pentoxifylline In Pediatric Acute Lymphoblastic Leukemia During Induction (PTX-II)

Ramón Óscar González-Ramella, Ph.D

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Acute Lymphoblastic Leukemia

Treatments: Drug: Pentoxifylline Plus Chemotherapy; Drug: Placebo Plus Chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT02451774

IICIA -PTX02

Details and patient eligibility

About

Recent advances in acute lymphoblastic leukemia treatment are based on a cytotoxic drug combination. Measurement of minimal residual disease in bone marrow samples at day 14 of treatment is the most powerful early predictive indicator of further relapse, and it can be applied practically to all patients with acute lymphoblastic leukemia. Even more so, it has been observed that patients who present negative minimal residual disease in bone marrow samples at day 7 during induction have a better prognosis than those achieving this at day 14.

Relapse represents the main cause of treatment failure that related in the extreme with resistance to apoptosis, defining the latter as the principal mechanism of programmed cell death; it is also related with the induction of leukemic cells to senescent arrest.

Pentoxifylline is a methyl-xanthine byproduct considered an unspecific inhibitor of phosphodiesterase. It inhibits nuclear factor-kappa-beta activation by different mechanisms and stimulates apoptosis induced by different drugs; thus, it can optimize the antineoplastic effect of actual treatments in order to increase the apoptosis of leukemic cells. This effect might improve the prognosis of these patients.

Evaluate the safety and effect of Pentoxifylline together with antineoplastic drugs in order to study increased apoptosis and decreased senescence during the remission induction phase in pediatric patients with newly diagnosed acute lymphoblastic leukemia. To achieve this propose, we will divide patients in two groups, who will receive pentoxifylline or placebo depending on the group, in addition to conventional treatment according to the protocol standard chemotherapy schema for pediatric patients with acute lymphoblastic leukemia at our institution during the remission induction phase. In addition, we will test whether the study group exerts an impact on reaching remission earlier as compared with the control group.

Full description

This study will be controlled, double-blind clinical trial versus placebo, with random assignment to evaluate the effect of pentoxifylline on apoptosis and senescence of leukemic blasts from remission induction in pediatric patients with newly diagnosed acute lymphoblastic leukemia, as well as to address pentoxifylline efficacy and safety in this group of patients.

Enrollment: 44 estimated patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pediatric and teenaged patients of both genders ≤18 years of age with newly diagnosed acute lymphoblastic leukemia in accordance with French-American-British criteria and under immunophenotypical classification and paired within the risk-classification group.
• Patients with ≥20 kg of weight at the time of treatment assignment.
• Patients who are able to swallow the medicine
• Patients agreeing to enter the protocol by the signing of informed consent by the parent
• Patients who could give their assent to enter the protocol
• The parent or guardian must be able to read.

Exclusion criteria

• Patients with treatment adherence of ≥80 percent
• Patients or their parents who decide to abandon the study or who withdraw consent for participation
• Patients who present grade III or higher adverse event.
• Patients previously treated with chemotherapy and/or radiotherapy
• History of peptic acid disease or gastrointestinal bleeding
• Known pentoxifylline intolerance and general intolerance to xanthine, caffeine or theophylline
• Patients in treatment with anticoagulants, Cimetidine, Ciprofloxacin, or Theophylline
• Patients with Down syndrome
• Patients with several bleeding or extensive retinal hemorrhage, several cardiac arrhythmias (paroxysmal supraventricular tachycardia, congenital atrioventricular block, arrhythmias associated with congenital heart disease, digital poisoning, and patients after cardiac surgery, hypoxia, hypercapnia, and electrolyte disturbances)
• Patients with hypotension
• Several liver failures
• Bleeding diathesis (for bleeding disorders or anticoagulant medication)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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44 participants in 2 patient groups, including a placebo group

Pentoxifylline Plus Chemotherapy

Experimental group

Description:

Pentoxifylline: 10-20 milligrams per kilogram, doses daily by oral, for 30 days. Chemotherapy: Prednisone, Vincristine, Daunorubicin, L-asparaginase, Cyclophosphamide, Cytarabine, 6-Mercaptopurine, Methotrexate, Hydrocortisone and Cytarabine

Treatment:

Drug: Pentoxifylline Plus Chemotherapy

Placebo Plus Chemotherapy

Placebo Comparator group

Description:

Placebo: double blind period, one doses daily for 30 days. Chemotherapy: Prednisone, Vincristine, Daunorubicin, L-asparaginase, Cyclophosphamide, Cytarabine, 6-Mercaptopurine, Methotrexate, Hydrocortisone and Cytarabine

Treatment:

Drug: Placebo Plus Chemotherapy