Cognitive Aftereffects of Neurotoxicity in Children and Young Adults With Relapsed/Refractory Hematologic Malignancies Who Receive CAR T-cell Therapy

Lymphoma Clinical Trial

Official title:

Investigation of the Cognitive Aftereffects of Neurotoxicity in Children and Young Adults With Relapsed/Refractory Hematologic Malignancies Who Receive CAR T-cell Therapy

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05237986
• Other study ID #: 10000631
• Secondary ID: 000631-C
• Status: Suspended
• Start date: May 8, 2024
• Est. completion date: April 30, 2027

Study information

• Verified date: March 21, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: CAR T-cell therapy is a promising new treatment for blood cancers. During treatment, a person s T-cells are genetically changed to kill cancer cells. Researchers want to learn more about the effects of potential problems that may be associated with this treatment. We are specifically interested in learning if and how this treatment may affect the brain or your thinking skills. Objective: To learn if CAR T-cell therapy can affect how children and adults think, process, and remember things. Eligibility: People aged 5-35 who have blood cancer that has not responded to treatment, or the blood cancer has come back after treatment, and who will receive CAR T-cell therapy. Caregivers are also needed. All participants must be able to speak and read in English or Spanish. Design: Participants will be screened with a medical history. Information from participants medical records will be collected. Participants will take tests at home or at NIH to see how well they think, read, learn, remember, reason, and pay attention. The tests will be both computerized and paper/pencil. They will take less than 1 hour to complete. Participants and a parent/adult observer will complete a 5-minute Background Information Form and a checklist of nervous system symptoms. If participants are 5 years or older, they will participate in activities to test their ability to do different thinking tasks, like answer questions, complete puzzle patterns, and remember things. Participants and their caregivers will complete questions to see if they are having specific symptoms related to receiving CAR T-cells. The questions will assess their well-being and needs. The questions will take less than 1 hour to complete. Some tests and questions will be repeated at different time points in the study. Participation will last for up to 3 years.

Description:

Background: - Chimeric antigen receptor (CAR) T-cell immunotherapy has rapidly emerged as a successful and breakthrough treatment in pediatric and adult hematologic malignancies. However, significant toxicities can complicate the therapeutic successes of such therapy, including neurologic toxicity associated with cytokine release syndrome (CRS). - There is a critical need to characterize the subacute and long-term neurocognitive outcomes of participants undergoing CAR T-cell therapies and to compare the results across trials, some of which are first-in-human studies. It is unknown how acute toxicity affects attention, learning, memory, processing speed, and higher order cognition in participants who are cured of their cancer and survive for many years. Information about subacute and long-term neurocognitive sequelae would help determine whether the acute toxicity of specific CAR T-cell therapies needs to be treated and prevented aggressively or whether it is fully reversible without specific intervention. Objective: -To evaluate subacute changes in working memory in children and young adults with relapsed/refractory leukemia or lymphoma at 2 months post CAR T-cell therapy Eligibility: - Children and young adults (age >= 5 and <=35 years old) with relapsed/refractory leukemias or lymphomas scheduled to have CAR T-cell therapy and their caregivers (informants). - Participants who can speak and read in English or Spanish Design: - This is a multi-center pilot trial to study the neurocognitive effects of CAR T-cell therapy. - Eligible participants will be seen in one of the enrolling sites. - Neurocognitive evaluations will be conducted using a computerized test battery (Cogstate) and other paper/pencil tests that assess cognitive processes known to be most affected in participants treated for leukemia or lymphomas as well as patient-reported and observer-reported outcome measures. Participants with the disease and their informants will be enrolled in this study during the preparation of participants for CAR T-cell therapy and followed for up to 3 years post CAR infusion.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 60
• Est. completion date: April 30, 2027
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

• INCLUSION CRITERIA:
• Participants with disease
• Participants are diagnosed with relapsed/refractory leukemias or lymphomas, and are scheduled to receive CAR T-cell treatment in one of the enrolling sites
• Age >= 5 and <=35 years old
• Participant must have an eligible caregiver (informant) who is willing to complete assessments about the participant of this study
• Participant must be able to speak and understand English or Spanish
• Participants must have access to a computer or tablet
• Participant or parent/guardian must be able to understand and willing to sign a written consent document
• Caregivers (informants)
• Participants must be able to speak and read in English or Spanish
• Participants who are caregivers for participants with disease addressed above
• Age >= 18 years old
• Participants must have access to a computer or tablet
• Participant is able to understand and willing to sign a written consent document EXCLUSION CRITERIA: None

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia
• Lymphoma
• Neurotoxicity Syndromes

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	Children s Hospital of Los Angeles	Los Angeles	California
United States	Seattle Children s Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate subacute changes in working memory in children and young adults with relapsed/refractory leukemia or lymphoma at 2 months post CAR T-cell therapy	The subacute changes in working memory (as measured by Cogstate One-Back reaction time standardized score) from baseline to 2-month post-infusion will be determined for each participant and the paired difference will be tested for a change from zero using a paired t-test. If the paired difference is not consistent with a normal distribution, then a Wilcoxon signed rank test may be used instead.	2 months post CAR T-cell infusion
Secondary	To evaluate subacute changes in additional neurocognitive domains in children and young adults with relapsed/refractory leukemia or lymphoma at 2 months post CAR T-cell therapy	The subacute changes in neurocognitive outcomes (reaction time, visual attention, learning and memory, working memory, and executive function) and daily functioning (everyday executive functioning, adaptive behavior, physical and mental health symptoms) from baseline to 2-month post-infusion will be determined for each participant and the paired difference will be tested for a change from zero using a paired t-test. If the paired difference is not consistent with a normal distribution, then a Wilcoxon signed rank test may be used instead.	3 years post CAR T-cell infusion

External Links

•   NIH Clinical Center Detailed Web Page