Treatment of Leukemia and Lymphoma in Children With Ataxia Telangiectasia

Treatment of Leukemia and Lymphoma in Children With Ataxia Telangiectasia- A Retrospective Study

Ataxia telangiectasia (A-T) is a multisystem disease with diverse manifestations, including progressive neurodegeneration, immunodeficiency, respiratory disease, and genomic instability. One of the most important features of A-T is the increased predisposition to cancer, especially to lymphoid malignancies. Patients with A-T are generally excluded from collaborative clinical trials, their treatment outcomes and toxicity profiles have rarely been reported, and little is currently known concerning the treatment intensity required to provide a reasonable balance between efficacy and toxicity. The aims of this study are to build a large international de-identified database of children with A-T treated for leukemia and lymphoma, to investigate epidemiology and outcome of treatment, toxicity profiles and risk factors which impact outcome, in order to eventually enable the generation of data-based treatment recommendations for this population.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Leukemia; Ataxia Telangiectasia

Detailed Description

Ataxia telangiectasia (A-T) is a multisystem disease with diverse manifestations, including progressive neurodegeneration, immunodeficiency, respiratory disease, and genomic instability. A-T is caused by biallelic mutations in the ATM gene, a major activator of the cellular response to DNA double strand breaks. One of the most important features of A-T is the increased predisposition to cancer. Lymphoid malignancies represent the majority of cancers. The treatment of cancer in children with A-T is extremely challenging, due to severe co-morbidities and a significantly increased risk of cancer therapy-related toxicities. Patients with A-T are generally excluded from collaborative clinical trials, their treatment outcomes and toxicity profiles have rarely been reported, and little is currently known concerning the treatment intensity required to provide a reasonable balance between efficacy and toxicity. The optimal treatment approach is controversial; some advocate treatment by standard chemotherapeutic protocols, while others advise initial protocol modifications with chemotherapy dose reductions. Due to the rarity of this disorder, there is an unmet need for an international collaboration for data collection concerning treatment, toxicity and outcome in children with cancer and A-T. Data will be collected from patient files, including patient characteristics and history, AT manifestations, malignancy characteristics, treatment, chemotherapy doses, treatment response, toxicity and outcome.

The aims of the study are to build a large international de-identified database of children with A-T treated for leukemia and lymphoma, to investigate epidemiology and outcome of treatment, toxicity profiles and risk factors which impact outcome, in order to eventually enable the generation of data-based treatment recommendations for this population.

This study will not involve the use of specimens or participant contact. All the data required have already been collected during the treatment of the participants, and is available in patient records.

• Study Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

Study Locations

• Israel
  • Petah Tikva, Israel, 4920235
    • Recruiting
    • Schneider Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children and young adults diagnosed with ataxia telangiectasia and leukemia or lymphoma

Description

Inclusion Criteria:

• Individuals diagnosed with ataxia telangiectasia and leukemia or lymphoma
• Age 0-21

Exclusion Criteria:

-Age greater than 21 years

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	Assess 5 and 3-year event-free survival	5 years
Overall survival	Assess 5 and 3-year overall survival	5 years
Cumulative incidence of relapse	Assess 5-year cumulative incidence of leukemia/lymphoma relapse	5 years
Cumulative incidence of treatment-related mortality	Assess 2-year cumulative incidence of treatment-related mortality	2 years
Cumulative incidence of second malignancies	Assess 5-year cumulative incidence of second malignancies	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cause and timing of death	Determine cause of death and timing of death in relation to specific elements of leukemia/lymphoma therapy (by questionnaire)	5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	2 years

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Collaborators: International BFM Study Group; Israeli Society for Pediatric Hematology-Oncology
• Investigators: Principal Investigator: Sarah Elitzur, MD, Schneider Children's Medical Center, Israel

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2019
• Primary Completion (Anticipated): October 28, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: July 21, 2019
• First Submitted That Met QC Criteria: July 29, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): October 1, 2021
• Last Update Submitted That Met QC Criteria: September 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neurologic Manifestations; Genetic Diseases, Inborn; Dyskinesias; DNA Repair-Deficiency Disorders; Neurocutaneous Syndromes; Cerebellar Diseases; Primary Immunodeficiency Diseases; Spinocerebellar Ataxias; Lymphoma; Leukemia; Ataxia; Telangiectasis; Cerebellar Ataxia; Ataxia Telangiectasia
• Other Study ID Numbers: 0132-19-RMC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No