Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers

NCT02830724 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 16013116-C-0131
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

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. ...

Conditions

Pancreatic Cancer; Renal Cell Cancer; Breast Cancer; Melanoma; Ovarian Cancer

Keywords

Metastatic Solid Cancers; Renal Cell Cancer; Cell Therapy; CAR T-Cells; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of treatment-related adverse events

  Grade and type of toxicity per dose level; fraction of patients who experience a DLT at a given dose level, and number and grade of each type of DLT

  From time of cell infusion to two weeks after cell infusion

• Response rate

  Percentage of patients who have a clinical response (PR+CR) to treatment (objective tumor regression)

  6 weeks and 12 weeks following administration of the cell product, then every 3 months x3, then every 6 months x 2 years, then per PI discretion

Secondary Outcomes (1)

• Frequency and severity of treatment-related adverse events

  6 weeks ( plus or minus 2 weeks) following administration of the cell product

Study Arms (2)

1/Phase I

EXPERIMENTAL

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-hCD70 CAR transduced PBL + high-dose aldesleukin

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

2/Phase II

EXPERIMENTAL

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-hCD70 CAR transduced PBL + high-dose aldesleukin

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

Interventions

Fludarabine DRUG

For Phase I, Days -7 to -5: Dose Level 1: 25 mg/m(2)/day x 3 days IVPB Dose Level 2: 25 mg/m(2)/day x 3 days IVPB Dose Level 3: 25 mg/m(2)/day x 3 days IVPB Dose Level 4: 25 mg/m(2)/day x 3 days IVPB Dose Level 5: 25 mg/m(2)/day x 5 days IVPB Dose Level 6: 25 mg/m(2)/day x 5 days IVPB For Phase II, Days -7 to -3: 25 mg/m(2)/day x 5 days IVPB

1/Phase I; 2/Phase II

Aldesleukin DRUG

Aldeskeukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum 9 doses).

1/Phase I; 2/Phase II

Anti-hCD70 CAR transduced PBL BIOLOGICAL

Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-5 days after the last dose of fludarabine).

1/Phase I; 2/Phase II

Cyclophosphamide DRUG

For Phase I, Days -7 and -6: Dose Level 1: 15 mg/kg/day x 2 days IV Dose Level 2: 15 mg/kg/day x 2 days IV Dose Level 3: 15 mg/kg/day x 2 days IV Dose Level 4: 15 mg/kg/day x 2 days IV Dose Level 5: 30 mg/kg/day x 2 days IV Dose Level 6: 60 mg/kg/day x 2 days IV For Phase II, Days -7 and -6: 60 mg/kg/day x 2 days IV

1/Phase I; 2/Phase II

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 sexes must be willing to practice birth control from the time of enrollment on this study and for 12 months after the last dose of combined chemotherapy for women and for four months after treatment for men.
• 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.
• NOTE: Certain malignancies may secrete hormones that produce false positive pregnancy tests. Serial blood testing (e.g. HCG measurements) and/ or ultrasound may be performed for clarification.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• 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. doi: 10.1016/j.ejca.2005.05.005.

  PMID: 16043348 BACKGROUND

• 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.

  PMID: 22401771 BACKGROUND

• 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.

  PMID: 8120384 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pancreatic Neoplasms; Carcinoma, Renal Cell; Breast Neoplasms; Melanoma; Ovarian Neoplasms

Interventions

Cyclophosphamide; fludarabine; aldesleukin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• James C Yang, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI SB Immunotherapy Recruitment Center

CONTACT

(866) 820-4505; IRC@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 13, 2016
• Study Start: April 6, 2017
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03-20

Locations

US (1)