Clinical trial NCT01005537: Cyclophosphamide, Autologous Lymphocytes, and Aldesleukin in Treating Patients With Metastatic Melanoma
Official title: Single Patient Study to Evaluate Cellular Adoptive Immunotherapy Using Autologous Lymphocytes Following Cyclophosphamide Conditioning for a Single Patient With Metastatic Melanoma
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-11-01
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapy, such as cellular adoptive immunotherapy using autologous lymphocytes, may stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Giving cyclophosphamide together with autologous lymphocytes and aldesleukin may be an effective treatment for metastatic melanoma.

PURPOSE: This phase I/II trial is studying the side effects of giving cyclophosphamide together with autologous lymphocytes and aldesleukin and to see how well it works in treating patients with metastatic melanoma.

Detailed description: OBJECTIVES:

Primary

* Assess the safety and toxicity of cellular adoptive immunotherapy with autologous tumor-infiltrating lymphocytes (TIL) following cyclophosphamide conditioning and post-infusion aldesleukin (IL-2) in patients with metastatic melanoma.
* Assess the duration of in vivo persistence of adoptively transferred lymphocytes.

Secondary

* Evaluate the antitumor effect of adoptively transferred autologous TIL following cyclophosphamide conditioning and post-infusion IL-2 in these patients.

OUTLINE: Patients receive cyclophosphamide IV on days -3 and -2 and autologous tumor-infiltrating lymphocytes (TIL) IV on day 0. Beginning 6 hours after TIL infusion, patients receive high-dose aldesleukin (IL-2) IV three times daily on days 0-5 (for up to 14 doses) OR low-dose IL-2 subcutaneously twice daily on days 0-14 (for up to 28 doses). Patients may then receive two additional courses of TILs and low-dose IL-2 (with or without cyclophosphamide), if indicated.

After completion of study treatment, patients are followed up periodically.

Eligibility criteria: Inclusion Criteria

* Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease.
* 18 to 75 years of age and able to tolerate high-dose cyclophosphamide
* Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, CT scan).
* For patients receiving HD-IL-2, normal cardiac stress test within 182 days prior to enrollment is required of all patients over 50 years old or those with an abnormal ECG, any history of cardiac disease, a family history of cardiac disease, hypercholesterolemia or hypertension.
* For leukapheresis, patients must meet the following criteria (any exceptions to this will require prior approval by the Apheresis director and Principal Investigator):

  * Pulse: \>45 or \< 120
  * Weight: \>45 kg
  * Temperature: \<38C (\<100.4 F)
  * WBC: \>3,000
  * HCT: \>30%
  * Platelets: \>100,000
* ADDITIONAL INCLUSION CRITERIA FOR T CELL INFUSION

Exclusion Criteria

* Significant cardiovascular abnormalities as defined by any one of the following:

  * congestive heart failure,
  * clinically significant hypotension,
  * symptoms of coronary artery disease,
  * presence of cardiac arrhythmias on EKG requiring drug therapy
  * ejection fraction \< 50 % (echocardiogram or MUGA)
* Patients with active infections or oral temperature \> 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Cassian Yee, MD
role: PRINCIPAL_INVESTIGATOR
References: