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Protocol Details

A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced with a CD70-Binding Chimeric Antigen Receptor to Patients with CD70-Expressing Cancers

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

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)

None

Intervention(s)

Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Aldesleukin
Biological/Vaccine: Anti-hCD70 CAR transduced PBL

Supporting Site

National Cancer Institute

Background:

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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Eligibility

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.


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Citations:

Diegmann J, Junker K, Gerstmayer B, Bosio A, Hindermann W, Rosenhahn J, von Eggeling F. Identification of CD70 as a diagnostic biomarker for clear cell renal cell carcinoma by gene expression profiling, real-time RT-PCR and immunohistochemistry. Eur J Cancer. 2005 Aug;41(12):1794-801.

Jilaveanu LB, Sznol J, Aziz SA, Duchen D, Kluger HM, Camp RL. CD70 expression patterns in renal cell carcinoma. Hum Pathol. 2012 Sep;43(9):1394-9. doi: 10.1016/j.humpath.2011.10.014. Epub 2012 Mar 7.

Bowman MR, Crimmins MA, Yetz-Aldape J, Kriz R, Kelleher K, Herrmann S. The cloning of CD70 and its identification as the ligand for CD27. J Immunol. 1994 Feb 15;152(4):1756-61.

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Contacts:

Principal Investigator

Referral Contact

For more information:

James C. Yang, M.D.
National Cancer Institute (NCI)



NCI SB Immunotherapy Recruitment Center
National Cancer Institute (NCI)

(866) 820-4505
IRC@nih.gov

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
(866) 820-4505
ncisbirc@mail.nih.gov

Clinical Trials Number:

NCT02830724

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