Treatment of Leukemia and Lymphoma in Children With Ataxia Telangiectasia

• Conditions: Ataxia Telangiectasia; Leukemia; Lymphoma

• Registration Number: NCT04037189
• Lead Sponsor: Rabin Medical Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2019-07-21
• Study Start: 2019-07-28
• Study First Submitted QC: 2019-07-29
• Study First Posted: 2019-07-30
• Status Verified: 2021-08
• Last Update Submitted: 2021-09-30
• Last Update Posted: 2021-10-01
• Primary Completion: 2021-10-28
• Study Completion: 2021-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

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

Exclusion Criteria

-Age greater than 21 years

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Schneider Children's Medical Center; 🇮🇱 Petah Tikva, Israel