Ex Vivo Drug Sensitivity Testing and Mutation Profiling

Recurrent Childhood Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Personalized Ex Vivo Drug Screening and Genomics Profiling to Guide Individualized Treatments for Children With Relapsed or Refractory Solid Tumors and Leukemias

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03860376
• Other study ID #: 1186919
• Secondary ID: 8LA05
• Status: Completed
• Start date: February 21, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: May 2023
• Source: Florida International University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is a prospective, non-randomized feasibility study. Freshly isolated tumor cells from patients will be screened using state-of-the-art viability assay designed for ex vivo high-throughput drug sensitivity testing (DST). In addition, genetic information will be obtained from cancer and normal (germline) tissue and correlated with drug response. This study will provide the platform for informing treating physician about individualized treatment options. The main outcome of this study will be the proportions of the patients whose treatment was guided by the personalized medicine approach.

Description:

PRIMARY OBJECTIVE: The primary objective of the study is to determine feasibility of providing pediatric cancer patients with access to personalized treatment options and clinical management recommendations based on ex vivo drug sensitivity testing (DST) and genomic profiling. SECONDARY OBJECTIVE: The secondary objective of the study is to compare individual outcomes (response and disease-free survival) in patients with pediatric cancers treated with DST-guided therapy as compared to non-DST guided (conventional) therapy. EXPLORATORY OBJECTIVE: To explore associations between genetic abnormalities in malignancies and ex vivo drug response.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 21 Years

Eligibility

Inclusion Criteria:

• Patients aged 21 years or younger at the time of enrollment on this study of any gender, race or ethnicity.
• Subjects with suspected or confirmed diagnosis of recurrent or refractory cancer
• Subjects who are scheduled for or have recently had biopsy or tumor excised (solid tumors) or bone marrow aspirate (blood cancers)
• Subjects willing to have a blood draw or buccal swab done for the purposes of genetic testing
• Subjects or their parents or legal guardians willing to sign informed consent
• Subjects aged 7 to 17 willing to sign assent

Exclusion Criteria:

• Subjects who do not have malignant tissue available and accessible
• The amount of excised malignant tissue is not sufficient for the ex vivo drug testing and/or genetic profiling.
• Patients with newly diagnosed tumors and tumors that have high (>90%) cure rate with safe standard therapy.

Related Conditions & MeSH terms

• Ependymoma
• Gliosarcoma
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Lymphoma
• Neoplasms, Germ Cell and Embryonal
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrence
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Recurrent Childhood Brain Tumor
• Recurrent Childhood Brainstem Glioma
• Recurrent Childhood Ependymoma
• Recurrent Childhood Gliosarcoma
• Recurrent Childhood Large Cell Lymphoma
• Recurrent Childhood Lymphoblastic Lymphoma
• Recurrent Childhood Rhabdomyosarcoma
• Recurrent Childhood Soft Tissue Sarcoma
• Refractory Childhood Acute Lymphoblastic Leukemia
• Refractory Childhood Hodgkin Lymphoma
• Refractory Childhood Malignant Germ Cell Neoplasm
• Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Rhabdomyosarcoma
• Sarcoma

Locations

Country	Name	City	State
United States	Nicklaus Children's Hospital	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Florida International University	Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

Acanda De La Rocha AM, Fader M, Coats ER, Espinal PS, Berrios V, Saghira C, Sotto I, Shakya R, Janvier M, Khatib Z, Abdella H, Bittle M, Andrade-Feraud CM, Guilarte TR, McCafferty-Fernandez J, Salyakina D, Azzam DJ. Clinical Utility of Functional Precisio — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients that receive DST-guided treatmens	This study will be considered successful (feasibility demonstrated) if it is possible to choose and initiate a monotherapy or combination drug regimen based on functional and/or genomics data within 4 weeks in at least 16 out of 25 patients (64%).; To achieve at least 90% power, the null hypothesis will be rejected when at least 16 out of 25 patients receive treatment recommendations through functional and/or genomics data within 4 weeks on the study.; With that outcome, we would have 95% confidence that the true feasibility rate is at least 30% (95% CI: 0.425, 1).	Up to 4 years
Secondary	Assessing Objective Response Rate	We will assess changes in cohort Objective Response Rate (ORR) by comparing ORR in patients treated with FPM-guided therapy versus ORR in patients treated with non-FPM guided conventional therapy (standard of care)	Up to 4 years
Secondary	Assessing Progression-Free Survival (PFS)	We will assess changes in cohort PFS by comparing PFS in patients treated with FPM-guided therapy versus PFS in patients treated with non-FPM guided conventional therapy (standard of care)	Up to 4 years
Secondary	Assessing Previous vs Trial PFS Ratio (PFS2/PFS1)	We will assess changes in PFS from each patient's previous treatment versus their PFS from the treatment assigned during the trial. Assessments will be made both in the FPM-guided cohort and the non-FPM-guided conventional therapy cohort. Analysis will include both the raw ratio as well as the number of incidences of 30% improved PFS on trial versus previous regimen (PFS2/PFS1 > 1.3x).	Up to 4 years