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Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, August 2009
First Received: February 10, 2006   Last Updated: August 5, 2009   History of Changes
Sponsors and Collaborators: M.D. Anderson Cancer Center
Chiron Corporation
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00338377
  Purpose

The primary objective will be to determine whether patients receiving adoptively transferred, tumor antigen-specific T cells in combination with dendritic cells and high dose IL-2 have sustained persistence of infused T cells compared to patients treated with T cells and high dose IL-2 alone. Secondary endpoints will include evaluations for tumor response and studies to determine whether dendritic cells enhance the infused T cells' anti-tumor activity and their ability to migrate to the tumor site. In addition, researchers will evaluate the characteristics of the infused T cells that correspond with effectiveness in vivo.


Condition Intervention Phase
Melanoma
Biological: Dendritic Cell Immunization
Drug: Cyclophosphamide
Drug: Fludarabine
Biological: T Cells
Biological: Interleukin-2
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title: Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Clinical Response (CR) [ Time Frame: Clinical Evaluation during first 70 Days, CT Scan at 6-8 weeks (+/- 7 days) after cell infusion. ] [ Designated as safety issue: No ]

Estimated Enrollment: 83
Study Start Date: February 2006
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Chemotherapy + IL-2 plus T-cells: Experimental Drug: Cyclophosphamide
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
Drug: Fludarabine
25 mg/m^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
Biological: T Cells
On Days 0, 3x10^9 - 1x10^11 T cells by vein infusion over 30-60 minutes.
Biological: Interleukin-2
12-16 hours after completing the T cell infusion, all will receive high dose IL-2 on an inpatient basis at the standard dose of 720,000 IU/kg as an intravenous bolus over approximately a 15 minute period every 8-16 hours for up to 15 doses on D-1-5, as tolerated.
Chemotherapy + IL-2 plus T-Cells + Vaccine: Experimental
Chemotherapy and IL-2 plus T-cells and the vaccine of dendritic cells
Biological: Dendritic Cell Immunization
1x10^7 to 1x10^8 MART-1 peptide-pulsed Dendritic Cells given by vein over 20-30 minutes approximately 4 hrs after receiving T cells.
Drug: Cyclophosphamide
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
Drug: Fludarabine
25 mg/m^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
Biological: T Cells
On Days 0, 3x10^9 - 1x10^11 T cells by vein infusion over 30-60 minutes.
Biological: Interleukin-2
12-16 hours after completing the T cell infusion, all will receive high dose IL-2 on an inpatient basis at the standard dose of 720,000 IU/kg as an intravenous bolus over approximately a 15 minute period every 8-16 hours for up to 15 doses on D-1-5, as tolerated.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Patients must have metastatic melanoma or stage III in-transit or regional nodal disease. (Turnstile I)
  2. Patients must receive an MRI/CT of the brain. If new lesions are present, patient must have definitive treatment. PI or his designee should make final determination regarding enrollment. (Turnstile I)
  3. Age greater than or equal to 12 years. (Turnstile I)
  4. Clinical performance status of ECOG 0-2. (Turnstile I)
  5. Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible. Patients receiving cytotoxic agents will be evaluated by the PI or his designee as to suitable eligibility. (Turnstile I)
  6. Patients with a negative pregnancy test (urine or serum) must be documented at screening for women of childbearing potential. (Turnstile I)
  7. Patients must be HLA-A2 for cohort A. (Turnstile II-Chemotherapy/Cell Infusion-Inclusion Criteria)
  8. Patients must have adequate TIL available as described in Appendix B. (Turnstile II)
  9. Patients must have measurable metastatic melanoma. (Turnstile II - Chemotherapy/Cell Infusion -Inclusion Criteria).
  10. Patients may have a maximum of 2 brain lesions which measure </= 1cm each. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  11. Patients of both genders must practice birth control for four months after receiving the preparative regimen. Patients must have a documented negative pregnancy test (urine or serum) for women who have menstruation in the past 12 months and without sterilization surgery. (Turnstile II)
  12. Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, IUD, or sponge plus spermicide. Abstinence is an acceptable form of birth control. (Turnstile II)
  13. Clinical performance status of ECOG 0 - 2 at the time of chemotherapy infusion. (Turnstile II - Chemotherapy/Cell Infusion-Inclusion Criteria).
  14. Absolute neutrophil count greater than or equal to 1000/mm3. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  15. Platelet count greater than or equal to 100,000/mm3. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  16. Hemoglobin greater than or equal to 8.0 g/dl. (Turnstile II - Chemotherapy/Cell Infusion).
  17. Serum ALT less than three times the upper limit of normal. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  18. Serum creatinine less than or equal to 1.6 mg/dl. (Turnstile II - Chemotherapy/Cell Infusion-Inclusion Criteria).
  19. Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl. (Turnstile II - Chemotherapy/Cell Infusion - Inclusion Criteria).
  20. Patients randomized to receive the DC arm of Cohort A will have the following tests: Donor infectious disease panel must be performed which includes the following tests: Hepatitis B surface antigen (HBsAg), Anti-Hepatitis B core antibody (HBC Abs),Anti-Hepatitis C Virus antibody (HCV Ab), Anti-Human Immunodeficiency Virus (HIV) antibody (HIV ½ Ab), Anti-Human T cell lymphotrophic Virus (HTLV) antibody (HTLV I/II Ab), Rapid Plasma Reagen (RPR), Cytomegalovirus antibody (CMV), HCV/HIV Nucleic Acid Test, West Nile Virus Nucleic Acid Test, Chagas Disease, and Sickledex.
  21. A stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion. (Turnstile II - Chemotherapy/Cell Infusion-Inclusion Criteria).
  22. Pulmonary function tests (FEV1>65% or FVC>65%of predicted) within 6 months of lymphodepletion.

(Turnstile II - Chemotherapy/Cell Infusion - Inclusion Criteria).

Exclusion Criteria:

  1. Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system. PI or designee shall make the final determination regarding appropriateness of enrollment. (Turnstile I - Screening Exclusion Criteria).
  2. Patients who are pregnant or nursing. (Turnstile I)
  3. Has had prior systemic cancer therapy within the past four weeks at the time of the start of the lymphodepletion regimen. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  4. Women who are pregnant will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  5. Any active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, such as abnormal stress test and/or abnormal PFT. PI or his designee shall make the final determination regarding appropriateness of enrollment.(Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  6. Any form of primary or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (> 500/mm3), WBC (> 3,000/mm3) or absence of opportunistic infections. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  7. Require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 30 days, or have used topical or inhalational steroids in the past 2 weeks prior to lymphodepletion. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  8. Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe or contraindicated. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00338377

Contacts
Contact: Patrick Hwu, MD 713-792-2921 phwu@mdanderson.org
Contact: Ralph Freedman, MD 713-792-2933 rfreedman@mdanerson.org

Locations
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Patrick Hwu, MD     713-792-2921     phwu@mdanderson.org    
Principal Investigator: Patrick Hwu, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
Chiron Corporation
Investigators
Principal Investigator: Patrick Hwu, MD U.T. M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: U.T.M.D. Anderson Cancer Center ( Patrick Hwu, MD/Professor )
Study ID Numbers: 2004-0069
Study First Received: February 10, 2006
Last Updated: August 5, 2009
ClinicalTrials.gov Identifier: NCT00338377     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Melanoma
Regional nodal disease
Dendritic Cell Immunization
Lymphodepletion
Adoptive Cell Transfer
T Cells
Vaccine
Cyclosphosphamide
Cytoxan
Neosar
Dendritic Cells
Tumor Infiltrating Lymphocytes
TIL Cells
MART Peptide
Fludarabine
Fludarabine Phosphate
Fludara
Proleukin
IL-2
Interleukin-2

Study placed in the following topic categories:
Antimetabolites
Anti-Infective Agents
Immunologic Factors
Cyclophosphamide
Melanoma
Anti-Retroviral Agents
Nevus, Pigmented
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Analgesics
Alkylating Agents
Anti-HIV Agents
Fludarabine monophosphate
Immunosuppressive Agents
Antiviral Agents
Neuroendocrine Tumors
Neuroectodermal Tumors
Aldesleukin
Interleukin-2
Analgesics, Non-Narcotic
Fludarabine
Nevus
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents
Antirheumatic Agents

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Cyclophosphamide
Melanoma
Anti-Retroviral Agents
Sensory System Agents
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Nevi and Melanomas
Analgesics
Alkylating Agents
Anti-HIV Agents
Neoplasms by Histologic Type
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Aldesleukin
Interleukin-2
Analgesics, Non-Narcotic
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 02, 2009