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

NCT02706392 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: 9330NCI-2015-01753RG92150452R01CA114536
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Experienced Adverse Events

  Will be graded according to Common Terminology Criteria for Adverse Events. Outcome will be reported as a count of participants that experienced adverse events in each arm.

  Within 35 days of receptor tyrosine kinase-like orphan receptor 1 positive chimeric antigen receptor-T cell infusion

Secondary Outcomes (5)

• Number of Participants With Persistence of Adoptively Transferred Receptor Tyrosine Kinase-like Orphan Receptor 1 Positive Chimeric Antigen Receptor-T Cells

  Up to 28 days after the T cell infusion

• Number of Participants Biopsied With Detectable CD3 T-cells

  Up to 48 days post infusion

• Objective Response Rate of Complete Remission and Partial Remission

  Up to 1 year

• Progression Free Survival

  Up to 1 year

• Overall Survival

  Up to 1 year

Study Arms (1)

Treatment (ROR1 CAR-specific autologous T-lymphocytes)

EXPERIMENTAL

Patients receive chemotherapy comprising fludarabine phosphate and cyclophosphamide as determined by the referring physician in consultation with the protocol PI. Beginning within 36-96 hours after completion of lymphodepleting chemotherapy, patients receive ROR1 CAR-specific autologous T-lymphocytes 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.

Other: Laboratory Biomarker Analysis; Biological: ROR1 CAR-specific Autologous T-Lymphocytes

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ROR1 CAR-specific autologous T-lymphocytes)

ROR1 CAR-specific Autologous T-Lymphocytes BIOLOGICAL

Given IV

Also known as: Autologous ROR1-CAR-T Cells, Chimeric Anti-ROR1 T-cell Receptor-expressing Autologous T-lymphocytes, ROR1-CAR-T

Treatment (ROR1 CAR-specific autologous T-lymphocytes)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CLL who are beyond first remission and who have failed combination chemoimmunotherapy with regimens containing a purine analogue and anti-CD20 antibody, or who have failed tyrosine kinase or phosphatidylinositol 3 (PI3) kinase inhibitors, or who were not eligible for or declined such therapy; patients with fludarabine refractory disease are eligible
• Mantle cell lymphoma patients who are beyond first remission and previously treated with chemoimmunotherapy; patients who have relapsed following autologous hematopoietic cell transplant (HCT) are eligible
• ALL patients who have relapsed or have residual disease following treatment with curative intent; ALL patients must have ROR1 expressed on \> 90% of the leukemia blasts to be eligible
• Confirmation of diagnosis by internal pathology review of initial or subsequent biopsy or other pathologic material at the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)
• Evidence of ROR1 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen
• Karnofsky performance status \>= 70%
• Negative pregnancy test for women of childbearing potential; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
• Fertile male and female patients must be willing to use a contraceptive method before, during, and for at least two months after the T cell infusion
• Ability to understand and provide informed consent
• Patients with non-small cell lung cancer that is metastatic or inoperable and who have been treated with at least one line of prior therapy or declined conventional therapy
• Patients with known epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations must have been treated on at least one line of molecularly targeted therapy (e.g., erlotinib, crizotinib)
• Patients must have measurable disease by at least one of the criteria below:
• Extra skeletal disease that can be accurately measured in at least one dimension as \>= 10 mm with conventional computed tomography (CT) techniques as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Skeletal or bone-only disease measurable by fludeoxyglucose F 18 (FDG) positron emission tomography (PET) imaging
• ROR1 expression in \> 20% of the primary tumor or metastasis by immunohistochemistry (IHC)

You may not qualify if:

• Treatment with other investigational agent(s) within 30 days of planned lymphodepletion
• Patients requiring ongoing daily corticosteroid therapy at a dose of \> 15 mg of prednisone per day (or equivalent); pulsed corticosteroid use for disease control is acceptable
• Active autoimmune disease requiring immunosuppressive therapy
• Serum creatinine \> 2.5 mg/dL
• Serum glutamic oxaloacetic transaminase (SGOT) \> 5 x upper limit of normal
• Bilirubin \> 3.0 mg/dL
• Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with a forced expiratory volume in 1 second (FEV1) of =\< 65% or diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) \< 40% will be excluded
• Significant cardiovascular abnormalities as defined by any one of the following: congestive heart failure, clinically significant hypotension, symptomatic coronary artery disease, or a documented ejection fraction of \< 45%; any patient with an ejection fraction (EF) of 45-49% must receive clearance by a cardiologist to be eligible for the trial
• Patients who are human immunodeficiency virus (HIV) seropositive
• Uncontrolled active infection (bacterial, viral, fungal, mycobacterial) not responding to treatment with intravenous antibiotics, antiviral or antifungal agents, or long-term treatment with oral agents
• Women who are breast-feeding
• Patients who have contraindication to cyclophosphamide chemotherapy
• Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to enrollment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases
• Absolute neutrophil count (ANC) \< 1000/mm\^3

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• Osorio-Rodriguez DA, Camacho BA, Ramirez-Segura C. Anti-ROR1 CAR-T cells: Architecture and performance. Front Med (Lausanne). 2023 Feb 17;10:1121020. doi: 10.3389/fmed.2023.1121020. eCollection 2023.

  PMID: 36873868 DERIVED

• Srivastava S, Furlan SN, Jaeger-Ruckstuhl CA, Sarvothama M, Berger C, Smythe KS, Garrison SM, Specht JM, Lee SM, Amezquita RA, Voillet V, Muhunthan V, Yechan-Gunja S, Pillai SPS, Rader C, Houghton AM, Pierce RH, Gottardo R, Maloney DG, Riddell SR. Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade. Cancer Cell. 2021 Feb 8;39(2):193-208.e10. doi: 10.1016/j.ccell.2020.11.005. Epub 2020 Dec 24.

  PMID: 33357452 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. David Maloney
• Organization: Fred Hutchinson Cancer Center

dmaloney@fredhutch.org

2066675616

Study Officials

• David Maloney

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Clinical Research Division

Study Record Dates

• First Submitted: March 1, 2016
• First Posted: March 11, 2016
• Study Start: March 16, 2016
• Primary Completion: May 17, 2021
• Study Completion: September 28, 2021
• Last Updated: August 31, 2022
• Results First Posted: August 31, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)