NCT02830724 · National Cancer Institute (NCI)
Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Cyclophosphamide
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
DRUG
Fludarabine
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
DRUG
Aldesleukin
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).
BIOLOGICAL
Anti-hCD70 CAR transduced PBL
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).
Primary outcome measures
Frequency and severity of treatment-related adverse events
Time frame: From time of cell infusion to two weeks after cell infusion
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
Response rate
Time frame: 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
Percentage of patients who have a clinical response (PR+CR) to treatment (objective tumor regression)
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 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
- 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.
Where
- Bethesda, Maryland
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 16, 2026 · Source of record for eligibility and locations