NCT02706392

Genetically Modified T-Cell Therapy in Treating Patients With Advanced ROR1+ Malignancies

Phase I Study of Adoptive Immunotherapy for Advanced ROR1+ Malignancies With Defined Subsets of Autologous T Cells Engineered to Express a ROR1-Specific Chimeric Antigen Receptor

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of genetically modified T-cell therapy in treating patients with receptor tyrosine kinase-like orphan receptor 1 positive (ROR1+) chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), stage IV non-small cell lung cancer (NSCLC), or triple negative breast cancer (TNBC) that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Genetically modified therapies, such as ROR1 specific chimeric antigen receptor (CAR) T-cells, are taken from a patient's blood, modified in the laboratory so they specifically may kill cancer cells with a protein called ROR1 on their surfaces, and safely given back to the patient after conventional therapy. The "genetically modified" T-cells have genes added in the laboratory to make them recognize ROR1.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety of adoptive T cell therapy using ex vivo expanded autologous cluster of differentiation (CD)8+ and CD4+ ROR1 CAR-T cells for patients with advanced ROR1+ hematologic (Cohort A) and epithelial (Cohort B) malignancies. SECONDARY OBJECTIVES: I. To determine duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells. II. To determine trafficking of adoptively transferred T cells traffic to the bone marrow or other tumor site and function in vivo. III. To determine preliminary antitumor activity of the adoptive transfer of ROR1 CAR-T cells in patients with measurable tumor burden prior to T cell transfer. OUTLINE: This is a dose escalation study of ROR1 CAR-specific autologous T-lymphocytes. Patients receive chemotherapy comprising fludarabine phosphate and cyclophosphamide as determined by the referring physician in consultation with the protocol principal investigator (PI). Beginning within 36-96 hours after completion of lymphodepleting chemotherapy, patients receive ROR1 CAR-specific autologous T-lymphocytes intravenously (IV) over 20-30 minutes. Patients may receive a second infusion of ROR1 CAR-specific autologous T-lymphocytes with or without additional cytoreductive therapy at the same (for those that received the highest cell dose) or up to the next highest dose level and there is persistent disease, there were no toxicities attributed to the first infusion, and the patient is at least 21 days from the first T cell infusion. After completion of study treatment, patients are followed up for at least 15 years.

Conditions

• Hematopoietic and Lymphoid Cell Neoplasm
• Malignant Solid Neoplasm
• Metastatic Lung Non-Small Cell Carcinoma
• Metastatic Triple-Negative Breast Carcinoma
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Mantle Cell Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Stage III Lung Non-Small Cell Cancer AJCC v7
• Stage IIIA Lung Non-Small Cell Cancer AJCC v7
• Stage IIIB Lung Non-Small Cell Cancer AJCC v7
• Stage IV Breast Cancer AJCC v6 and v7
• Stage IV Lung Non-Small Cell Cancer AJCC v7
• Unresectable Lung Non-Small Cell Carcinoma

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	ROR1 CAR-specific Autologous T-Lymphocytes	Given IV

Timeline

• Start date: 2016-03-16
• Primary completion: 2021-05-17
• Completion: 2021-09-28
• First posted: 2016-03-11
• Last updated: 2022-08-31
• Results posted: 2022-08-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study