This study is currently recruiting participants.
Number
16-C-0131
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Max Age: 72
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Fetuses;Children
Keywords
Metastatic Solid Cancers; Renal Cell Cancer; Cell Therapy; CAR T-Cells; Immunotherapy
Recruitment Keyword(s)
None
Condition(s)
Pancreatic Cancer; Renal Cell Cancer; Breast Cancer; Melanoma; Ovarian Cancer
Investigational Drug(s)
anti-hCD70 CAR transduced PBL Aldesleukin
Investigational Device(s)
Intervention(s)
Drug: Cyclophosphamide Drug: Fludarabine Drug: Aldesleukin Biological/Vaccine: Anti-hCD70 CAR transduced PBL
Supporting Site
National Cancer Institute
In a new cancer therapy, researchers take a person s blood, select a certain white blood cell to grow in the lab, and then change the genes of these cells using a virus. The cells are then given back to the person. This is called gene transfer. For this study, researchers will modify the person s white blood cells with anti-CD70.
Objectives:
To see if a gene transfer with anti-CD70 cells can safely shrink tumors and to be certain the treatment is safe.
Eligibility:
Adults age 18 and older diagnosed with cancer that has the CD70-expressing cancer.
Design:
Participants will be screened with medical history, physical exam, scans, and other tests. They may by admitted to the hospital. Leukapheresis will be performed. For this, blood is removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.
Eligible participants will have an intravenous catheter placed in their upper chest. Over several days, they will get chemotherapy drugs and the anti-CD70 cells. They will recover in the hospital.
Participants will take an antibiotic for 6 months after treatment. They will repeat leukapheresis.
Participants will visit the clinic every 1-3 months for the first year after treatment, every 6 months for the second year, and then as determined by their physician. Follow-up visits will take 1-2 days. At each visit, participants will have lab tests, imaging studies, and a physical exam.
Throughout the study, blood will be taken and participants will have many tests to determine the size and extent of their tumor and the treatment s impact.
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INCLUSION CRITERIA: -For Phase I: Evaluable, unresectable cancer expressing CD70 as assessed by immunohistochemistry of resected tissue (greater than or equal to 2+ CD70 positive on greater than or equal to 50% of cancer cells, or greater than or equal to 1+ CD70 positive on greater than or equal to 75% of cancer cells). -For Phase II: Measurable (per RECIST v1.1 criteria), unresectable cancer expressing CD70 as assessed by immunohistochemistry of resected tissue (greater than or equal to 2+ CD70 positive on greater than or equal to 50% of cancer cells, or greater than or equal to 1+ CD70 positive on greater than or equal to 75% of cancer cells). -Confirmation of the diagnosis of cancer by the NCI Laboratory of Pathology. -Patients must have previously received at least one standard therapy for their cancer (if available) and have been either non-responders (progressive disease) or have recurred. -Patients with 3 or fewer brain metastases that are less than or equal to 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. -Age greater than or equal to 18 years and less than or equal to 72 years. -Clinical performance status of ECOG 0 or 1 -Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment. -Women of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus. -Serology --Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) --Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. -Hematology --ANC greater than 1000/mm(3) without the support of filgrastim --WBC greater than or equal to 2500/mm(3) --Platelet count greater than or equal to 80,000/mm(3) --Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off. -Chemistry --Serum ALT/AST less than or equal to 5.0 times ULN --Serum creatinine less than or equal to 1.6 mg/dL --Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL. -Patients must have completed any prior systemic therapy at the time of enrollment. Note: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to grade 1 or less. -Ability of subject to understand and the willingness to sign a written informed consent document. -Willing to sign a durable power of attorney. -Subjects must be co-enrolled on the NCI-SB cell harvest protocol 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols). EXCLUSION CRITERIA: -Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. -Concurrent systemic steroid therapy. -Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses. -Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). -History of hematopoietic autoimmune disease or any autoimmune disease requiring immunosuppressive measures. -Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities). -History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin. -History of coronary revascularization or ischemic symptoms. -For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%. -For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50% predicted. -Patients who are receiving any other investigational agents.
-For Phase I: Evaluable, unresectable cancer expressing CD70 as assessed by immunohistochemistry of resected tissue (greater than or equal to 2+ CD70 positive on greater than or equal to 50% of cancer cells, or greater than or equal to 1+ CD70 positive on greater than or equal to 75% of cancer cells).
-For Phase II: Measurable (per RECIST v1.1 criteria), unresectable cancer expressing CD70 as assessed by immunohistochemistry of resected tissue (greater than or equal to 2+ CD70 positive on greater than or equal to 50% of cancer cells, or greater than or equal to 1+ CD70 positive on greater than or equal to 75% of cancer cells).
-Confirmation of the diagnosis of cancer by the NCI Laboratory of Pathology.
-Patients must have previously received at least one standard therapy for their cancer (if available) and have been either non-responders (progressive disease) or have recurred.
-Patients with 3 or fewer brain metastases that are less than or equal to 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
-Age greater than or equal to 18 years and less than or equal to 72 years.
-Clinical performance status of ECOG 0 or 1
-Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.
-Women of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.
-Serology
--Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental
treatment and more susceptible to its toxicities.)
--Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
-Hematology
--ANC greater than 1000/mm(3) without the support of filgrastim
--WBC greater than or equal to 2500/mm(3)
--Platelet count greater than or equal to 80,000/mm(3)
--Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off.
-Chemistry
--Serum ALT/AST less than or equal to 5.0 times ULN
--Serum creatinine less than or equal to 1.6 mg/dL
--Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL.
-Patients must have completed any prior systemic therapy at the time of enrollment.
Note: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to grade 1 or less.
-Ability of subject to understand and the willingness to sign a written informed consent document.
-Willing to sign a durable power of attorney.
-Subjects must be co-enrolled on the NCI-SB cell harvest protocol 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols).
EXCLUSION CRITERIA:
-Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
-Concurrent systemic steroid therapy.
-Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.
-Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
-History of hematopoietic autoimmune disease or any autoimmune disease requiring immunosuppressive measures.
-Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
-History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
-History of coronary revascularization or ischemic symptoms.
-For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.
-For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50% predicted.
-Patients who are receiving any other investigational agents.
Principal Investigator
Referral Contact
For more information: