Phase 2
Completed N=12
Prospective Randomized Comparative Study of Cell Transfer Therapy Using CD8+-Enriched Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Compared to High-Dose Aldesleukin in M...
Source: ClinicalTrials.gov NCT01118091 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Jun 2013
Primary outcomePrimary: Response Rate — 0; 0; 1; 1 Participants
Summary
Background:
- Adoptive cell therapy involves taking white blood cells called lymphocytes from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient to allow the cells to attack the tumor. Because this process is lengthy and difficult to perform, researchers have been developing improved means of performing adoptive cell therapy. Researchers are now interested in comparing adoptive cell therapy with the standard treatment for metastatic melanoma (skin cancer).
Objectives:
- To compare the effectiveness of adoptive cell therapy with standard high-dose aldesleukin as a treatment for metastatic melanoma.
Eligibility:
* Individuals 18 years of age or older who have been diagnosed with metastatic melanoma and have not previously received aldesleukin therapy or cell therapy for their disease.
* Participants must have at least one tumor that can be easily removed as part of the treatment procedure.
Design:
* Participants will be screened with a full medical history, physical examination, blood and urine tests, and imaging scans to evaluate tumor size and treatment options.
* Participants will be separated into two groups, in which one group will have adoptive cell therapy and one will have aldesleukin treatment.
* Adoptive Cell Therapy
* Participants will have a tumor sample taken in order to collect white blood cells for treatment. Participants whose tumors do not provide sufficient white blood cells may be switched to the aldesleukin-only treatment group.
* The white blood cells will be grown in the laboratory for several weeks.
* Prior to receiving cell therapy, participants will receive chemotherapy for 7 days to improve the chances of successful treatment.
* Participants will have cell therapy followed by high-dose aldesleukin treatment every 8 hours for up to 5 days. This treatment will be followed by 1 to 2 weeks of recovery time as an inpatient at the clinical center.
* Participants will be evaluated at 12 weeks following the start of the study, every 2 to 3 months for the first year, every 6 months for the next 5years, and then yearly thereafter..
* Standard Aldesleukin Treatment
* Participants will have high-dose aldesleukin treatment every 8 hours for up to 5 days (one cycle of treatment), and will have a second cycle of treatment 7 to 10 days after the first cycle.
* If tests show that the tumors have grown, participants will be offered the chance to have additional cycles of aldesleukin, or begin a cell therapy treatment.
* Participants will be evaluated at 12 weeks following the start of the study, every 2 to 3 months for the first year, every 6 months for the next 5years, and then yearly thereafter.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Response Rate |
0; 0; 1; 1; 6; 4 | — |
| PRIMARY Progression Free Survival |
307; 0; 0; 130; 0; 88 | — |
| SECONDARY Toxicity |
7; 5 | — |
Eligibility Criteria
- INCLUSION CRITERIA:
- Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation. The lesion must be of at least 2cm in diameter that can be surgically removed with minimal morbidity (defined as any operation for which expected hospitalization is less than or equal to 7 days).
- Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.
- No prior high-dose aldesleukin therapy at a dose of greater than or equal to 600,000 IU/kg.
- Greater than or equal to 18 years of age.
- Willing to practice birth control during treatment and for four months after receiving all protocol related therapy.
- Life expectancy of greater than three months.
- Willing to sign a durable power of attorney.
- Able to understand and sign the Informed Consent Document.
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Hematology:
- Absolute neutrophil count greater than 1000/mm^3 without support of filgrastim
- Normal White blood cell (WBC) (> 3000/mm^3).
- Hemoglobin greater than 8.0 g/dl
- Platelet count greater than 100,000/mm^3
k. Serology:
- Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for hepatitis B antigen, or hepatitis C antibody or antigen.
l. Chemistry:
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three times the upper limit of normal.
- Calculated creatinine clearance estimated glomerular filtration rate(eGFR) > 50 ml/min.
- Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.
m. More than four weeks must have elapsed since any prior systemic therapy at the time the time of randomization, and patients' toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo). Patients must have stable or progressing disease after prior treatment. Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria.
n. Six weeks must have elapsed since any prior anti-CTLA4 antibody therapy to allow antibody levels to decline.
o. Patients who have previously received any cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) antibody and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.
EXCLUSION CRITERIA
- Prior cell transfer therapy which included a non-myeloablative or myeloablative chemotherapy regimen.
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- Systemic steroid therapy requirement.
- Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and Acquired Immunodeficiency Syndrome (AIDS)).
- 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 any of the ag
Data sourced from ClinicalTrials.gov (NCT01118091). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.