Treated Blood Cells, Cyclophosphamide, Fludarabine Phosphate, and Aldesleukin in Treating Patients With Cancer

NCT01212887 | Terminated Phase 1

• 5 other identifiers: CDR0000685060CRUK-PH1/105CRUK-MFEzEUDRACT-2005-004085-16EU-21070
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Placing a gene into T cells may improve the body's ability to recognize cancer cells and build an immune response to fight cancer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as aldesleukin, may stimulate the immune system in different ways and stop cancer cells from growing. Giving specially treated T cells together with cyclophosphamide, fludarabine phosphate, and aldesleukin may kill more tumor cells. PURPOSE: This phase I clinical trial is studying the side effects and best dose of treated T cells when given together with cyclophosphamide, fludarabine phosphate, and aldesleukin in treating patients with cancer.

Conditions

Breast Cancer; Colorectal Cancer; Gastric Cancer; Lung Cancer; Ovarian Cancer; Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific; recurrent colon cancer; stage IIIA colon cancer; stage IIIB colon cancer; stage IIIC colon cancer; stage IV colon cancer; stage IVB colon cancer; recurrent rectal cancer; stage IIIA rectal cancer; stage IIIB rectal cancer; stage IIIC rectal cancer; stage IVA rectal cancer; stage IVB rectal cancer; recurrent gastric cancer; stage IV gastric cancer; recurrent pancreatic cancer; stage III pancreatic cancer; stage IV pancreatic cancer; recurrent breast cancer; stage IIIC breast cancer; stage IV breast cancer; extensive stage small cell lung cancer; recurrent non-small cell lung cancer; recurrent small cell lung cancer; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent ovarian epithelial cancer; recurrent ovarian germ cell tumor; stage IIIA ovarian epithelial cancer; stage IIIA ovarian germ cell tumor; stage IIIB ovarian epithelial cancer; stage IIIB ovarian germ cell tumor; stage IIIC ovarian epithelial cancer; stage IIIC ovarian germ cell tumor; stage IV ovarian epithelial cancer; stage IV ovarian germ cell tumor

Outcome Measures

Primary Outcomes (3)

• Percentage of patients (goal is 50%) who are evaluable for MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes survival

• Adverse event according to CTCAE version 3 criteria

• Dose of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes that gives the highest frequency in the circulation as measured by the primary assays (recommended phase II dose)

Secondary Outcomes (3)

• Presence of cells with a functional chimeric immune receptor on bCEA binding assay

• Partial response or complete response on CT scans at 6, 12, 24, and 52 weeks as defined by RECIST criteria

• Long-term follow up for insertional mutagenesis

Interventions

MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes BIOLOGICAL

aldesleukin BIOLOGICAL

cyclophosphamide DRUG

fludarabine phosphate DRUG

laboratory biomarker analysis OTHER

pharmacological study OTHER

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed malignancy * Metastatic or unresectable disease * Standard curative or palliative measures do not exist, are no longer effective, have been completed, or have been refused * CEA-positive tumor (either by immunohistochemistry or as demonstrated by elevated CEA \> 50 μg/L) * No primary brain tumor or brain metastases PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Life expectancy ≥ 3 months * Hemoglobin ≥ 10 g/dL * Platelet count ≥ 100 x 10\^9/L * Neutrophil count ≥ 2.0 x 10\^9/L * Lymphocyte count ≥ 1.0 x 10\^9/L * Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT/AST ≤ 5 times ULN * Alkaline phosphatase ≤ 5 times ULN * Calculated creatinine clearance OR isotope clearance measurement ≥ 50 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception 4 weeks prior to, during, and for 6 months after completion of study therapy (male patients must use barrier-method contraception) * LVEF ≥ 50% on MUGA scan (for patients receiving cyclophosphamide) * ECG and exercise ECG (or stress ECHO) normal (may be abnormal but not clinically significant) * Urine dipstick normal (may be abnormal but not clinically significant) * No medical high risk due to nonmalignant systemic disease including active uncontrolled infection * No known serologically positive hepatitis B, hepatitis C, HIV, or HTLV * No history of autoimmune disease * No inflammatory bowel disease * No concurrent congestive heart failure or prior history of NYHA class III-IV cardiac disease * No concurrent malignancies originating from other primary sites, except for adequately treated cone-biopsied carcinoma in situ of the cervix uteri or basal cell or squamous cell carcinoma of the skin * No other condition that, in the investigator's opinion, would make the patient an unsuitable candidate for the clinical trial PRIOR CONCURRENT THERAPY: * At least 30 days since prior and no concurrent participation in another clinical trial * At least 4 weeks since prior and no concurrent radiotherapy (except for palliative reasons \[i.e., control of bone pain\]) * At least 4 weeks since prior and no concurrent endocrine therapy, immunotherapy, or chemotherapy (6 weeks for nitrosoureas and mitomycin C) * No toxic manifestations of previous treatment, except for alopecia or certain grade 1 toxicities that, in the opinion of the investigator and CRUK (Cancer Research UK), would exclude the patient (e.g., grade 1 neuropathy or grade 1 fatigue) * No prior major thoracic and/or abdominal surgery from which the patient has not yet recovered * No prior bone marrow transplant or extensive radiotherapy to \> 25% of bone marrow * No concurrent systemic steroids or other immunosuppressive therapy * No other concurrent anticancer therapy or investigational drugs

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

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (1)

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Stomach Neoplasms; Lung Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Carcinoma, Ovarian Epithelial

Interventions

aldesleukin; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

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

Study Officials

• Robert E. Hawkins, MD

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2010
• First Posted: October 1, 2010
• Study Start: August 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: February 28, 2012

Record last verified: 2012-02

Locations

GB (1)