Gene-Modified Lymphocytes, High-Dose Aldesleukin, and Vaccine Therapy in Treating Patients With Progressive or Recurrent Metastatic Cancer

NCT00704938 | Terminated Phase 2 Results DMC

• 3 other identifiers: 080155NCI-08-C-0155NCI-P07215
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Gene-modified lymphocytes may stimulate the immune system in different ways and stop tumor cells from growing. High-dose aldesleukin may stimulate lymphocytes to kill tumor cells. Vaccines made from a gene modified virus and a person's dendritic cells may help the body build an effective immune response to kill tumor cells. Giving gene-modified lymphocytes together with high-dose aldesleukin and vaccine therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gene-modified lymphocytes together with high-dose aldesleukin and vaccine therapy works in treating patients with progressive or recurrent metastatic cancer.

Conditions

Kidney Cancer; Melanoma (Skin); Unspecified Adult Solid Tumor, Protocol Specific

Keywords

recurrent renal cell cancer; stage IV renal cell cancer; recurrent melanoma; stage IV melanoma; unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• Clinical Response (Complete Response + Partial Response)

  Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all lesions. Partial response is a 30% decrease in the sum of the longest diameter (LD) of target lesions.

  5 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  5 months

Study Arms (2)

anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC

EXPERIMENTAL

Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)

Biological: aldesleukin; Biological: anti-p53 T-cell receptor-transduced peripheral blood lymphocytes; Biological: autologous dendritic cell-adenovirus p53 vaccine; Biological: filgrastim; Drug: cyclophosphamide; Drug: fludarabine phosphate

anti-p53 TCR PBL + DC + IL-2: Other histology

EXPERIMENTAL

Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)

Biological: aldesleukin; Biological: anti-p53 T-cell receptor-transduced peripheral blood lymphocytes; Biological: autologous dendritic cell-adenovirus p53 vaccine; Biological: filgrastim; Drug: cyclophosphamide; Drug: fludarabine phosphate

Interventions

aldesleukin BIOLOGICAL

Intravenous (IV) aldesleukin 720,000 IU/kg every 8 hours for a maximum of 15 doses.

Also known as: Proleukin

anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC; anti-p53 TCR PBL + DC + IL-2: Other histology

anti-p53 T-cell receptor-transduced peripheral blood lymphocytes BIOLOGICAL

Intravenous (IV) anti-p53 TCR transduced PBL will be administered at a a dose of 1 x 10\^8 cells to 5 x 10\^10 cells.

anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC; anti-p53 TCR PBL + DC + IL-2: Other histology

autologous dendritic cell-adenovirus p53 vaccine BIOLOGICAL

Ad-p53 DC vaccine, up to 2 x 10\^8 ad-p53 DCs per dose will be administered subcutaneously, divided into 4 injections, one into each of the 4 extremities. Ad-p53 DCs will be administered subcutaneously on day 7 (± 2 days), day 14 (between day 14 and day 18), and day 28 (between day 25 and day 42) post T cell infusion.

anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC; anti-p53 TCR PBL + DC + IL-2: Other histology

filgrastim BIOLOGICAL

subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day).

Also known as: growth colony stimulating factor (GCSF)

anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC; anti-p53 TCR PBL + DC + IL-2: Other histology

cyclophosphamide DRUG

60mg/kg/day (Days-7,-6)

Also known as: Cytoxan

anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC; anti-p53 TCR PBL + DC + IL-2: Other histology

fludarabine phosphate DRUG

25mg/m\^2 (Days -5, -4, -3, -2, and -1)

Also known as: Fludara

anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC; anti-p53 TCR PBL + DC + IL-2: Other histology

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of metastatic cancer * Tumor overexpresses p53 as assessed by immunohistochemistry (i.e., ≥ 5% tumor cells stain positive for p53) * Biopsy must be available to evaluate p53 expression * Human leukocyte antigens 0201 (HLA-A\*0201) positive * Progressive or recurrent disease after prior standard therapy for metastatic disease * Patients with melanoma or renal cell cancer must have previously received aldesleukin * Patients with other histologies, not including hematologic malignancies, must have previously received first-line and second-line or higher systemic standard therapy (or effective salvage chemotherapy regimens) PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Life expectancy \> 3 months * Absolute neutrophil count \> 1,000/mm\^3 * White blood cell (WBC) \> 3,000/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin \> 8.0 g/dL * Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal * Serum creatinine ≤ 1.6 mg/dL * Total bilirubin ≤ 2.0 mg/dL (\< 3.0 mg/dL in patients with Gilbert's syndrome) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 4 months after completion of study treatment * Patients who have previously received ipilimumab or ticilimumab must have a normal colonoscopy with normal colonic biopsies * Human immunodeficiency virus (HIV) antibody negative * Hepatitis B antigen and hepatitis C antibody negative (unless antigen negative) * No primary immunodeficiency (e.g., severe combined immunodeficiency disease) * No active systemic infections * No history of severe immediate hypersensitivity reaction to any of the agents used in this study * No coagulation disorders * No myocardial infarction or cardiac arrhythmias * No history of coronary revascularization * No obstructive or restrictive pulmonary disease * No contraindications for high-dose aldesleukin administration * Left ventricular ejection fraction (LVEF) ≥ 45% in patients meeting any of the following criteria: * History of ischemic heart disease, * chest pain, * or clinically significant atrial and/or ventricular arrhythmias including, but not limited to, atrial fibrillation, * ventricular tachycardia, * or second- or third-degree heart block * At least 60 years of age * Forced expiratory volume 1 (FEV\_1) \> 60% predicted in patients meeting any of the following criteria: * Prolonged history of cigarette smoking (\> 20 pack/year within the past 2 years) * Symptoms of respiratory dysfunction * No other major medical illness of the cardiovascular, * respiratory, * or immune system PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * More than 4 weeks since prior and no concurrent systemic steroid therapy * More than 4 weeks since other prior systemic therapy * More than 6 weeks since prior ipilimumab

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

MeSH Terms

Conditions

Kidney Neoplasms; Melanoma; Carcinoma, Renal Cell

Interventions

aldesleukin; Filgrastim; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

This study was terminated prior to completing accrual due to the withdrawal of support from our collaborator.

Results Point of Contact

• Title: Steven A. Rosenberg, M.D.
• Organization: National Cancer Institute, National Institues of Health

sar@mail.nih.gov

301-496-4164

Study Officials

• Steven A. Rosenberg, MD, PhD

  NCI - Surgery Branch

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 24, 2008
• First Posted: June 25, 2008
• Study Start: June 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: October 28, 2015
• Results First Posted: August 14, 2012

Record last verified: 2015-09

Locations

US (1)