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

May 7, 2018 updated by: Ramón Óscar González-Ramella, Ph.D

SAFETY AND EFFICACY OF PENTOXIFYLLINE VERSUS PLACEBO ADMINISTERED AS APOPTOSIS INDUCTOR DURING REMISSION INDUCTION PHASE OF PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

44

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44340
        • Recruiting
        • Hospital Civil de Guadalajara "Dr. Juan I. Menchaca"
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Pentoxifylline Plus Chemotherapy

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
Drug: Pentoxifylline Plus Chemotherapy
Pentoxifylline 10 to 20 milligrams per kilogram, daily, for up to 32 days Chemotherapy: Prednisone 40 milligrams per square meter per day, orally, day 5-32. Vincristine 1.5 milligrams per square meter per week, intravenously, day 5, 12, 19, 26. Daunorubicin 25 milligrams per square meter per week, intravenously, days 5; 12. L-asparaginase 10,000 units for square meter, intramuscular, days 6, 8, 10, 12, 14, 16, 19, 21, 23. Cyclophosphamide 1000 milligrams per square meter per dose intravenously, day 26. Cytarabine 75 milligrams per square meter per dose intravenously, days 27-30, 34-37. 6-Mercaptopurine 60 milligrams per square meter per dose, orally, days 26-39, Mix: Methotrexate 8-12 milligrams, Hydrocortisone 16-24 milligrams and Cytarabine 24-36 milligrams, intrathecal, day 19.
Other Names:
  • Oxpentifylline
PLACEBO_COMPARATOR: Placebo Plus Chemotherapy
Placebo: double blind period, one doses daily for 30 days. Chemotherapy: Prednisone, Vincristine, Daunorubicin, L-asparaginase, Cyclophosphamide, Cytarabine, 6-Mercaptopurine, Methotrexate, Hydrocortisone and Cytarabine
Drug: Placebo Plus Chemotherapy
Placebo daily, for up to 32 days Chemotherapy: Prednisone 40 milligrams per square meter per day, orally, day 5-32. Vincristine 1.5 milligrams per square meter per week, intravenously, day 5, 12, 19, 26. Daunorubicin 25 milligrams per square meter per week, intravenously, days 5; 12. L-asparaginase 10,000 units for square meter, intramuscular, days 6, 8, 10, 12, 14, 16, 19, 21, 23. Cyclophosphamide 1000 milligrams per square meter per dose intravenously, day 26. Cytarabine 75 milligrams per square meter per dose intravenously, days 27-30, 34-37. 6-Mercaptopurine 60 milligrams per square meter per dose, orally, days 26-39, Mix: Methotrexate 8-12 milligrams, Hydrocortisone 16-24 milligrams and Cytarabine 24-36 milligrams, intrathecal, day 19.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Apoptosis measure by Flow Cytometry
Time Frame: Up to 28 days after initiation of chemotherapy for remission induction
Percentage of apoptotic cells by Flow Cytometry
Up to 28 days after initiation of chemotherapy for remission induction

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Senescence measure by Flow Cytometry
Time Frame: Up to 28 days after initiation of chemotherapy for remission induction.
Percentage of senescent blasts by Flow Cytometry
Up to 28 days after initiation of chemotherapy for remission induction.
Safety measure by Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Evaluate frequency adverse events with pentoxifylline up to 6 weeks
Percentage of adverse events grading table is a list of common terms and severity (intensity) of parameters used to describe adverse events occurring in Common Terminology Criteria for Adverse Events version 4.0
Evaluate frequency adverse events with pentoxifylline up to 6 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gene expression measure by Microarray and Semi-quantitative Polymerase Chain Reaction.
Time Frame: Up to 28 days after initiation of chemotherapy for remission induction.
Fold change by microarray and Semi-quantitative Polymerase Chain Reaction.
Up to 28 days after initiation of chemotherapy for remission induction.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ramón Óscar González-Ramella, Ph.D

Collaborators

Hospital Civil Juan I. Menchaca
Instituto de Investigacion en Cancer de la Infancia y la Adolescencia
Centro de Investigacion Biomedica de Occidente

Investigators

  • Principal Investigator: Ramón O. Gonzalez Ramella, PhD, Instituto de Investigacion de Cancer de la Infancia y la Adolescencia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (ANTICIPATED)

December 1, 2019

Study Completion (ANTICIPATED)

December 1, 2020

Study Registration Dates

First Submitted

February 9, 2015

First Submitted That Met QC Criteria

May 19, 2015

First Posted (ESTIMATE)

May 22, 2015

Study Record Updates

Last Update Posted (ACTUAL)

May 9, 2018

Last Update Submitted That Met QC Criteria

May 7, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IICIA -PTX02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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