Laboratory-Treated Autologous Peripheral Blood Lymphocytes, Aldesleukin, Cyclophosphamide, and Fludarabine in Treating Patients With Metastatic Melanoma - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00665470

Purpose

RATIONALE: Treating a patient's peripheral blood lymphocytes in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes to kill tumor cells.

Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving laboratory-treated autologous peripheral blood lymphocytes and aldesleukin after combination chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving laboratory-treated autologous peripheral blood lymphocytes together with aldesleukin after cyclophosphamide and fludarabine works in treating patients with metastatic melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Biological: aldesleukin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Study in Patients With Metastatic Melanoma Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of gp100 Reactive Peripheral Blood Lymphocytes (PBL) and High or Low Dose Aldesleukin

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Aldesleukin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response [ Designated as safety issue: No ]
Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Survival of infused cells [ Designated as safety issue: No ]

Estimated Enrollment:	65
Study Start Date:	December 2007
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Cohort I: Experimental Patients receive high-dose aldesleukin IV over 15 minutes every 8 hours beginning within 24 hours after PBL infusion and continuing for up to 5 days (maximum of 15 doses).	Biological: aldesleukin Given IV
Cohort II: Experimental Beginning within 24 hours after PBL infusion, patients receive low-dose aldesleukin SC once daily 5 days a week for up to 6 weeks.	Biological: aldesleukin Given IV

Detailed Description:

OBJECTIVES:

Primary

To determine whether treatment with autologous gp100:154-162-reactive peripheral blood lymphocytes and high- or low-dose aldesleukin after a nonmyeloablative, lymphocyte-depleting preparative regimen comprising cyclophosphamide and fludarabine phosphate results in clinical tumor regression in patients with metastatic melanoma.
To determine the toxicity of this regimen in these patients.

Secondary

To determine the survival of infused cells in these patients using analysis of the sequence of the variable region of the T-cell receptor or flow cytometry.

OUTLINE:

Lymphocyte-depleting preparative regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.
Autologous gp100-reactive peripheral blood lymphocyte (PBL) infusion: Patients receive autologous gp100:154-162-reactive PBL IV over 20-30 minutes on day 0. Beginning on day 1 or 2, patients receive filgrastim (G-CSF) subcutaneously (SC) once daily until blood counts recover.
Aldesleukin: Patients are assigned to 1 of 2 aldesleukin treatment cohorts (depending on their eligibility to receive high-dose aldesleukin).
- Cohort I (high-dose aldesleukin): Patients receive high-dose aldesleukin IV over 15 minutes every 8 hours beginning within 24 hours after PBL infusion and continuing for up to 5 days (maximum of 15 doses).
- Cohort II (low-dose aldesleukin): Beginning within 24 hours after PBL infusion, patients receive low-dose aldesleukin SC once daily 5 days a week for up to 6 weeks. Patients with a partial response to treatment or stable disease that subsequently progresses may receive up to one retreatment course (as above) beginning approximately 12 weeks after the last dose of aldesleukin.

PBL obtained during leukapheresis are evaluated for function and phenotype and may be tested by cytolysis assays, cytokine release, limiting dilution analysis, and by other experimental studies. Immunological monitoring comprises quantifying T cells reactive with HLA-matched tumor cells using established techniques, such as intracellular FACS, cytokine release assays, and Elispot assays. CD4 and CD8 T cells are measured and studies of cell persistence in the circulation are conducted using PCR assays. Samples of all infused cell products will be cryopreserved, and extensive retrospective analysis of infused cell phenotype and function will be performed to attempt to find in vitro characteristics of the infused cells which correlate with in vivo antitumor activity.

Analyses of PBL samples may also include evaluation of the activity, specificity, and telomere length of the infused PBL.

After completion of study therapy, patients are followed every 1-6 months until disease progression.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of metastatic melanoma
Measurable disease
Refractory to treatment with high-dose aldesleukin, if medically eligible to receive it
- Patients with ocular melanoma are not required to be refractory to high-dose aldesleukin
Must have gp100:154-162-reactive peripheral blood lymphocytes available (via leukapheresis performed on another Surgery Branch protocol)
HLA-A*0201 positive

PATIENT CHARACTERISTICS:

ECOG performance status 0-1 (for patients treated in the high-dose aldesleukin cohort) OR ECOG 0-2 (for patients treated in the low-dose aldesleukin cohort)
Life expectancy > 3 months
ANC > 1,000/mm³ (without filgrastim [G-CSF] support)
WBC > 3,000/mm³
Hemoglobin > 8.0 g/dL
Platelet count > 100,000/mm³
ALT and AST ≤ 2.5 times upper limit of normal
Creatinine ≤ 1.6 mg/dL
Total bilirubin ≤ 2.0 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)
HIV negative
Hepatitis B surface antigen or hepatitis C antibody negative
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 4 months after receiving the preparative regimen
Physically able to tolerate nonmyeloablative chemotherapy
FEV_1 > 60% predicted in patients with a prolonged history of cigarette smoking (i.e., 20 pk/yrs of smoking) or symptoms of respiratory dysfunction (for patients treated in the high-dose aldesleukin cohort)
LVEF > 45% (for patients treated in the high-dose aldesleukin cohort)
- Patients meeting any of the following criteria must undergo evaluation of LVEF (in order to be treated in the high-dose aldesleukin cohort):
  - Evidence of clinically significant atrial and/or ventricular arrhythmias including, but not limited to, atrial fibrillation, ventricular tachycardia, or second or third degree heart block
  - Age ≥ 60 years old
No history of coronary revascularization or ischemic symptoms (for patients treated in the high-dose aldesleukin cohort)
No active systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system, as evidenced by any of the following (for patients treated in the high-dose aldesleukin cohort):
- Positive stress thallium or comparable test
- Myocardial infarction
- Cardiac arrhythmias
- Obstructive or restrictive pulmonary disease
No primary immunodeficiency (e.g., severe combined immunodeficiency disease)
No opportunistic infections
No history of severe immediate hypersensitivity reaction to any of the agents used in this study

PRIOR CONCURRENT THERAPY:

More than 4 weeks since prior systemic therapy and recovered (except for toxicities such as alopecia or vitiligo)
More than 6 weeks since prior ipilimumab (MDX-010)
- Patients who were previously treated with MDX-010 must have a normal colonoscopy with normal colonic biopsies
Minor surgical procedures within the past 3 weeks allowed provided all toxicities have recovered to grade 1 or less
No concurrent systemic steroids

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00665470

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Udai S. Kammula, MD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	NCI - Center for Cancer Research ( Udai S. Kammula )
Study ID Numbers:	CDR0000594115, NCI-08-C-0104, P07210
Study First Received:	April 23, 2008
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00665470 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IV melanoma
recurrent melanoma

Study placed in the following topic categories:

Anti-Infective Agents
Anti-HIV Agents
Cyclophosphamide
Fludarabine monophosphate
Antiviral Agents
Recurrence
Melanoma
Neuroendocrine Tumors

Neuroectodermal Tumors
Aldesleukin
Anti-Retroviral Agents
Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Neuroepithelioma
Nevus
Fludarabine

Additional relevant MeSH terms:

Anti-Infective Agents
Neoplasms by Histologic Type
Anti-HIV Agents
Antineoplastic Agents
Neoplasms, Nerve Tissue
Antiviral Agents
Pharmacologic Actions
Melanoma

Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Aldesleukin
Anti-Retroviral Agents
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Nevi and Melanomas

ClinicalTrials.gov processed this record on September 11, 2009