Genetically Modified T-Cell Therapy in Treating Patients With Advanced ROR1+ Malignancies
Condition: 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
MeSH terms: Carcinoma; Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence
Intervention: Laboratory Biomarker Analysis; ROR1 CAR-specific Autologous T-Lymphocytes
Intervention description: Correlative studies; Given IV
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

        INCLUSION CRITERIA FOR PATIENTS WITH CLL, MCL OR ALL (COHORT A)

          -  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

        INCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B):

          -  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)

          -  Karnofsky performance status of >= 70%

          -  Patients must be off chemotherapy for a minimum of 3 weeks prior to start of
             treatment; targeted therapies must be stopped at least 3 days prior to start of
             lymphodepletion

          -  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

        INCLUSION CRITERIA FOR TNBC:

          -  Histologically confirmed diagnosis of metastatic TNBC; i.e. breast cancer that is
             estrogen receptor (ER) negative (=< 10%), progesterone receptor (PR) negative (=<
             10%), and human epidermal growth factor receptor 2 (HER2) negative (0 or 1+ by
             immunohistochemistry or negative for gene amplification by fluorescence in situ
             hybridization [FISH])

          -  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 CT techniques as defined by RECIST 1.1

               -  Skeletal or bone-only disease measurable by FDG PET imaging

          -  Patients must have received standard adjuvant, neoadjuvant, and/or metastatic
             chemotherapy per National Comprehensive Cancer Network (NCCN) or institutional
             practice; no maximum on number of prior systemic treatment regimens

          -  Patients may receive agents to protect against skeletal related complications such as
             zoledronic acid or denosumab

          -  ROR1 expression in > 20% of the primary tumor or metastasis by IHC

          -  Karnofsky performance status of >= 70%

          -  Patients must be off chemotherapy for a minimum of 3 weeks prior to planned
             leukapheresis

          -  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

        Exclusion Criteria:

        EXCLUSION CRITERIA FOR PATIENTS WITH CLL, MCL, OR ALL (COHORT A)

          -  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

        EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B):

          -  Absolute neutrophil count (ANC) < 1000/mm^3

          -  Hemoglobin (Hgb) < 9 mg/dl (transfusion permitted to achieve this)

          -  Platelet count < 75,000/mm^3

          -  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

          -  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 an
             FEV1 of =< 65% or 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 EF of
             45-49% must receive clearance by a cardiologist to be eligible for the trial

          -  Patients who are 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 breastfeeding

          -  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

        EXCLUSION CRITERIA FOR TNBC:

          -  ANC < 1000/mm^3

          -  Hgb < 9 mg/dl (transfusion permitted to achieve this)

          -  Platelet count < 75,000/mm^3

          -  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

          -  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 an
             FEV1 of =< 65% or 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 EF of
             45-49% must receive clearance by a cardiologist to be eligible for the trial

          -  Patients who are 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

          -  Breast-feeding women

          -  Patients who have contraindication to cyclophosphamide chemotherapy

          -  Has a 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) and have no evidence
             of new or enlarging brain metastases