Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and Sargramostim (GM-CSF) in Treating Advanced Solid Tumors

NCT01081808 | Terminated Phase 1 DMC

• 1 other identifier: RWH 111-32
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving autologous lymphocytes that have been treated in the laboratory with antibodies may stimulate the immune system to kill tumor cells. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving laboratory-treated autologous lymphocytes together with aldesleukin and GM-CSF may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated autologous lymphocytes when given together with aldesleukin and GM-CSF in treating patients with recurrent, refractory, or metastatic advanced solid tumors.

Conditions

Neoplasms; Tumors; Solid Tumors; Metastatic Cancer

Keywords

PhaseI; Solid Tumor; biomarkers; T cell; Cetuximab; Epidermal Growth Factor Receptor; Aldesleukin; Lymphocytes; Autologous; Recurrent; Refractory; Metastatic; Immunotherapy; Antibodies; Neoplasms by Site; Anti-Retroviral Agents; Therapeutic Uses; Anti-Infective Agents; Neoplasms by Histologic Type; Antineoplastic Agents; Antiviral Agents; Pharmacologic Actions; Carcinoma; Neoplasms

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of EGFRBi-armed autologous activated T-cells

  5 week regimen with 2 month follow up

Secondary Outcomes (6)

• Determine potential side effects of treating patients with Armed Activated T Cells (ATC)

  5 week regimen with 2 month follow up

• Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro

  5 week regimen with 2 month follow up

• Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy

  5 week regimen with 2 month follow up

• Overall survival

  5 week regimen wtih 2 month follow up

• Progression-free survival

  5 week regimen with 2 month follow up

Study Arms (1)

Armed Activated T Cells

OTHER

Activated T Cells (ATC) armed with the bispecific antibody OKT3 x Cetuximab (EGFRBi). ATC will be expanded for 14 days from a leukapheresis product, armed with EGFRBi, cryopreserved and infused in 8 divided doses. Patients will also receive low dose subcutaneous IL-2(3000,000 IU/m2/day) and GM-CSF (250ug/m2 twice per week)

Biological: EGFRBi-armed autologous activated T cells

Interventions

EGFRBi-armed autologous activated T cells BIOLOGICAL

EGFRBi-armed autologous activated T cells infused twice a week for 4 weeks for a total of 8 infusions. The doses of the armed ATC will be escalated at the dose levels of 5, 10, 20, and 40 billion armed ATC per infusion. Subcutaneous aldesleukin (300,000IU/m2/day) and Sargramostim (250 ug/m2 twice per week) both starting 3 days before the 1st infusion and ending 7 days after the last dose of armed ATC.

Also known as: ATC, IL-2, GM-CSF

Armed Activated T Cells

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed solid tumor type (ex. Head and Neck Squamous Cell Carcinoma, Colorectal, Pancreatic, Gastric, Esophageal, Renal, Prostate, Breast and Ovarian cancers, etc.); high risk, recurrent, refractory, or metastatic disease after ≥ 1 prior first-line regimen (chemotherapy or radiotherapy)
• Documented EGFR-positive disease (any expression level) by immunohistochemistry (IHC)
• No clinical evidence of active brain metastases; patients with brain metastases are eligible provided they have received definitive radiotherapy or chemotherapy and/or have undergone surgical resection for brain metastases
• No prior hematological malignancy
• Karnofsky performance status (PS) 60-100% OR RCOG PS 0-2
• Life expectancy ≥ 3 months
• Not pregnant or nursing
• Fertile patients must use contraception
• Granulocytes ≥ 1,000/mm3
• Platelet count ≥ 50,000/mm3
• Hemoglobin ≥ 8g/dL
• BUN ≤ 2.0 times normal
• Serum creatinine ≤ 2.0mg/dL
• Bilirubin ≤ 1.5 times normal (with or without liver metastases)
• Hepatitis B surface antigen and HIV negative

You may not qualify if:

• Serious medical or psychiatric illness that would preclude giving informed consent or receiving intensive treatment
• Recent myocardial infarction (within the past year)
• Current angina/coronary symptoms requiring medications
• Clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA results)
• Systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 m Hg; patients with elevated BP must have it controlled by anti-hypertensive medications for at least 7 days prior to the infusion
• Clinical evidence of active brain metastases
• Prior/Concurrent Therapy
• More than 4 weeks since prior chemotherapy or radiotherapy
• At least 4 weeks since prior cetuximab or small molecule EGFR-inhibitors including, but not limited to, gefitinib or erlotinib hydrochloride
• No concurrent radiotherapy
• No concurrent steroids except for treatment or adrenal failure, septic shock, or pulmonary toxicity or hormones for non-disease-related conditions(e.g., insulin for diabetes)

Sponsors & Collaborators

• Roger Williams Medical Center: lead

Study Sites (1)

Roger Willaims Medical Center

Providence, Rhode Island, 02908, United States

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Recurrence; Neoplasms by Site; Neoplasms by Histologic Type; Carcinoma

Interventions

Interleukin-2; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors

Study Officials

• Abby Maizel, MD,PhD

  Roger William Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: March 5, 2010
• Study Start: October 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: February 1, 2015
• Last Updated: March 25, 2015

Record last verified: 2015-03

Locations

US (1)