Clinical trial NCT02451774: Pentoxifylline In Pediatric Acute Lymphoblastic Leukemia During Induction
Official title: SAFETY AND EFFICACY OF PENTOXIFYLLINE VERSUS PLACEBO ADMINISTERED AS APOPTOSIS INDUCTOR DURING REMISSION INDUCTION PHASE OF PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Acute Lymphoblastic Leukemia
Keywords: pediatric
apoptosis
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
Collaborators: name: Instituto de Investigacion en Cancer de la Infancia y la Adolescencia
name: Hospital Civil Juan I. Menchaca
name: Centro de Investigacion Biomedica de Occidente
First posted: 2015-05-22
Enrollment: 44
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Apoptosis measure by Flow Cytometry
timeFrame: Up to 28 days after initiation of chemotherapy for remission induction
Secondary outcomes:
measure: Senescence measure by Flow Cytometry
timeFrame: Up to 28 days after initiation of chemotherapy for remission induction.
measure: Safety measure by Common Terminology Criteria for Adverse Events version 4.0
timeFrame: Evaluate frequency adverse events with pentoxifylline up to 6 weeks
Other outcomes:
measure: Gene expression measure by Microarray and Semi-quantitative Polymerase Chain Reaction.
timeFrame: Up to 28 days after initiation of chemotherapy for remission induction.
Locations:
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara "Dr. Juan I. Menchaca"
state: Jalisco
Study officials:
affiliation: Instituto de Investigacion de Cancer de la Infancia y la Adolescencia
name: Ramón O. Gonzalez Ramella, PhD
role: PRINCIPAL_INVESTIGATOR
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