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Therapeutic Autologous Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Stage IV Melanoma

Primary Purpose

Recurrent Melanoma, Stage IV Melanoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
therapeutic autologous lymphocytes
aldesleukin
immunohistochemistry staining method
biopsy
laboratory biomarker analysis
immunologic technique
polymerase chain reaction
Sponsored by
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease
  • Expression of HLA-A2, B44, or A3 as determined by Fred Hutchinson Cancer Research Center (FHCRC) human leukocyte antigen (HLA) typing lab
  • Zubrod performance status of 0-1
  • Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, CT scan)
  • Normal cardiac stress test within 182 days prior to enrollment is required of all patients over 50 years old or those with an abnormal electrocardiogram (ECG), any history of cardiac disease, a family history of cardiac disease, hypercholesterolemia or hypertension
  • FOR LEUKAPHERESIS:
  • Pulse > 45 or < 120
  • Weight >= 45 kg
  • White blood cell count (WBC) >= 3,000
  • Temperature =< 38C (=< 100.4 F)
  • Hematocrit (HCT) >= 30%
  • Platelets >= 100,000
  • FOR T CELL INFUSION: Patients must be willing and able to discontinue the use of all anti-hypertensive medications 24 hours prior to and during IL-2 therapy

Exclusion Criteria:

  • Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry
  • Serum creatinine > 1.6 mg/dL or Creatinine clearance < 75 ml/min
  • Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3x upper limit of normal
  • Bilirubin > 1.6 mg/dL
  • Prothrombin time > 1.5 x control
  • Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or carbon monoxide diffusing capacity (DLco) (corr for Hgb) < 75% will be excluded
  • 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 electrocardiograph (EKG) requiring drug therapy;
  • Ejection fraction < 50 % (echocardiogram or multi gated acquisition scan [MUGA])
  • Symptomatic central nervous system metastases greater than 1 cm at the time of therapy; patients with 1-2 asymptomatic, less than 1 cm brain/central nervous system (CNS) metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, than a repeat imaging will be performed if more than 3 weeks have elapsed from the last scan; patients will not be treated if CNS lesions are > 1 cm or if patient is symptomatic from brain metastasis
  • 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
  • Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell therapy)
  • Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be recently polymerase chain reaction (PCR)+ for hepatitis are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed immune system found in these infected patients and the possibility of premature death would compromise study objectives
  • FOR T CELL INFUSION: 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
  • FOR T CELL INFUSION: Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy
  • FOR T CELL INFUSION: Current treatment with steroids
  • FOR T CELL INFUSION: Patients must not be receiving any other experimental drugs within 3 weeks of the initiation of the protocol and must have recovered from all side effects of such therapy

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, immunosuppressive, lymphocytes)

Arm Description

All patients receive high-dose cyclophosphamide IV on days -3 and -2 and autologous antigen-specific cytotoxic CD8+ T-lymphocyte clones IV over 30-60 minutes on day 0. COHORT I: Beginning within 6 hours of T cell infusion, patients receive low-dose aldesleukin SC twice daily on days 0-14. COHORT II: Beginning within 6 hours of T cell infusion, patients receive high-dose aldesleukin IV 3 times daily on days 0-5.

Outcomes

Primary Outcome Measures

The identification of a CY/IL-2 regimen that is considered to be safe
The identification of a CY/IL-2 regimen (among those considered safe) which yields the greatest effect on the duration of in vivo persistence of adoptively transferred CTL clones

Secondary Outcome Measures

Full Information

First Posted
February 20, 2007
Last Updated
March 14, 2012
Sponsor
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00438984
Brief Title
Therapeutic Autologous Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Stage IV Melanoma
Official Title
Phase I Study To Evaluate Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following Cyclophosphamide Conditioning For Patients With Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Biological therapies, such as therapeutic autologous lymphocytes, may stimulate the immune system in different ways and stop tumor cells from growing. 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. Cyclophosphamide may also stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate white blood cells to kill tumor cells. Giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin may be an effective treatment for melanoma. PURPOSE: This phase I trial is studying the side effects of giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin in treating patients with stage IV melanoma
Detailed Description
PRIMARY OBJECTIVES: I. To assess the safety and toxicity of cellular adoptive immunotherapy in melanoma patients receiving autologous CD8+ antigen-specific T cell clones following cyclophosphamide conditioning and post-infusion IL-2. II. To assess the duration of in vivo persistence of adoptively transferred CD8+ T cell clones. SECONDARY OBJECTIVES: I. Evaluate the antitumor effect of adoptively transferred CD8+ antigenspecific cytotoxic t lymphocytes (CTL) clones following cyclophosphamide conditioning and post-infusion IL-2. OUTLINE: Patients are assigned 1of 2 treatment cohorts. All patients receive high-dose cyclophosphamide intravenously (IV) on days -3 and -2 and autologous antigen-specific cytotoxic CD8+ T lymphocyte clones IV over 30-60 minutes on day 0. COHORT I: Beginning within 6 hours of T cell infusion, patients receive low-dose aldesleukin subcutaneously (SC) twice daily on days 0-14. COHORT II: Beginning within 6 hours of T cell infusion, patients receive high-dose aldesleukin IV 3 times daily on days 0-5. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, 8 weeks, and every 3 months thereafter for up to 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy, immunosuppressive, lymphocytes)
Arm Type
Experimental
Arm Description
All patients receive high-dose cyclophosphamide IV on days -3 and -2 and autologous antigen-specific cytotoxic CD8+ T-lymphocyte clones IV over 30-60 minutes on day 0. COHORT I: Beginning within 6 hours of T cell infusion, patients receive low-dose aldesleukin SC twice daily on days 0-14. COHORT II: Beginning within 6 hours of T cell infusion, patients receive high-dose aldesleukin IV 3 times daily on days 0-5.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
therapeutic autologous lymphocytes
Other Intervention Name(s)
AL, Autologous Lymphocytes, autologous T cells
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
aldesleukin
Other Intervention Name(s)
IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Intervention Description
Given IV or SC
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Other Intervention Name(s)
immunohistochemistry
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
biopsy
Other Intervention Name(s)
biopsies
Intervention Description
Optional correlative studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
immunologic technique
Other Intervention Name(s)
immunological laboratory methods, laboratory methods, immunological
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
polymerase chain reaction
Other Intervention Name(s)
PCR
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
The identification of a CY/IL-2 regimen that is considered to be safe
Time Frame
Baseline, 4 weeks and 8 weeks
Title
The identification of a CY/IL-2 regimen (among those considered safe) which yields the greatest effect on the duration of in vivo persistence of adoptively transferred CTL clones
Time Frame
Baseline, 4 weeks and 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease Expression of HLA-A2, B44, or A3 as determined by Fred Hutchinson Cancer Research Center (FHCRC) human leukocyte antigen (HLA) typing lab Zubrod performance status of 0-1 Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, CT scan) Normal cardiac stress test within 182 days prior to enrollment is required of all patients over 50 years old or those with an abnormal electrocardiogram (ECG), any history of cardiac disease, a family history of cardiac disease, hypercholesterolemia or hypertension FOR LEUKAPHERESIS: Pulse > 45 or < 120 Weight >= 45 kg White blood cell count (WBC) >= 3,000 Temperature =< 38C (=< 100.4 F) Hematocrit (HCT) >= 30% Platelets >= 100,000 FOR T CELL INFUSION: Patients must be willing and able to discontinue the use of all anti-hypertensive medications 24 hours prior to and during IL-2 therapy Exclusion Criteria: Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry Serum creatinine > 1.6 mg/dL or Creatinine clearance < 75 ml/min Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3x upper limit of normal Bilirubin > 1.6 mg/dL Prothrombin time > 1.5 x control Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or carbon monoxide diffusing capacity (DLco) (corr for Hgb) < 75% will be excluded 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 electrocardiograph (EKG) requiring drug therapy; Ejection fraction < 50 % (echocardiogram or multi gated acquisition scan [MUGA]) Symptomatic central nervous system metastases greater than 1 cm at the time of therapy; patients with 1-2 asymptomatic, less than 1 cm brain/central nervous system (CNS) metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, than a repeat imaging will be performed if more than 3 weeks have elapsed from the last scan; patients will not be treated if CNS lesions are > 1 cm or if patient is symptomatic from brain metastasis 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 Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell therapy) Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be recently polymerase chain reaction (PCR)+ for hepatitis are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed immune system found in these infected patients and the possibility of premature death would compromise study objectives FOR T CELL INFUSION: 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 FOR T CELL INFUSION: Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy FOR T CELL INFUSION: Current treatment with steroids FOR T CELL INFUSION: Patients must not be receiving any other experimental drugs within 3 weeks of the initiation of the protocol and must have recovered from all side effects of such therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cassian Yee
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Therapeutic Autologous Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Stage IV Melanoma

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