Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
Prometheus Laboratories
Key Biologics, LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00338377
First received: February 10, 2006
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

The goal of this clinical research study is to learn if a vaccine prepared from special blood cells (dendritic cells) will improve the function of fighting immune cells (T cells) specific for melanoma. These special blood cells and immune cells will be taken from patient's blood and tissue and grown in the laboratory and then given back to the patient. Researchers will also study the ability of these cells to shrink or slow the growth of the metastatic melanoma when given with chemotherapy and Interleukin-2 (IL-2). Researchers will also study if this combination will help to control the disease if there is a BRAF mutation of the melanoma.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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: 159
Study Start Date: February 2006
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy + IL-2 plus T-cells
Cyclophosphamide 60 mg/kg/d by vein (IV) over 2 hours Days -7 and -6 (with Mesna) and Fludarabine 25 mg/m^2 IV daily Days -5 to -1 before T cell infusion. On Day 0, up to 1.5 x 10^11 T cells IV infusion over 30-60 minutes. Interleukin-2 12-16 hours after T cell infusion at standard dose of 720,000 IU/kg as intravenous bolus over 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26.
Drug: Cyclophosphamide
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
Other Names:
  • Cytoxan
  • Neosar
Drug: Fludarabine
25 mg/m^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Biological: T Cells
On Days 0, up to 1.5 x 10^11 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 Days 1-5 and 22-26 (+/- 7 days), as tolerated.
Other Names:
  • IL-2
  • Proleukin
Drug: Mesna
60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.
Other Names:
  • Sodium 2-mercaptoethanesulfonate
  • Mesnum
  • Mesnex
  • NSC-113891
Experimental: Chemotherapy + IL-2 plus T-Cells + Vaccine
Chemotherapy and IL-2 plus T-cells and the vaccine of dendritic cells received by vein (IV) about 4 hours after T-cells and again on Day 21 (+/- 7 days). Cyclophosphamide 60 mg/kg/d IV over 2 hours Days -7 and -6 (with Mesna) and Fludarabine 25 mg/m^2 IV daily Days -5 to -1 before T cell infusion. On Day 0, up to 1.5 x 10^11 T cells IV infusion over 30-60 minutes. Interleukin-2 12-16 hours after T cell infusion at standard dose of 720,000 IU/kg as intravenous bolus over 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26.
Biological: Dendritic Cell Immunization
1x10^7 to 2.5x10^8 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
Other Names:
  • Cytoxan
  • Neosar
Drug: Fludarabine
25 mg/m^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Biological: T Cells
On Days 0, up to 1.5 x 10^11 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 Days 1-5 and 22-26 (+/- 7 days), as tolerated.
Other Names:
  • IL-2
  • Proleukin
Drug: Mesna
60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.
Other Names:
  • Sodium 2-mercaptoethanesulfonate
  • Mesnum
  • Mesnex
  • NSC-113891

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 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 or PET/CT within 6 months of consenting. If new lesions are present, 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 Eastern Cooperative Oncology Group (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 must be HLA-A2 for cohort A. (Turnstile II-Chemotherapy/Cell Infusion-Inclusion Criteria)
  7. Patients must have adequate TIL available. (Turnstile II)
  8. Patients must have measurable metastatic melanoma. (Turnstile II - Chemotherapy/Cell Infusion -Inclusion Criteria).
  9. Patients may have brain lesions which measure </= 1cm each. Lesions that are >1 cm that have been treated with SRS and in the opinion of the PI or his designee no longer represents active disease will also be allowed. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  10. Patients of both genders must practice birth control for four months after receiving the preparative regimen. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  11. 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.
  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, intrauterine device (IUD), or sponge plus spermicide. Abstinence is an acceptable form of birth control. (Turnstile II)
  13. Pregnancy testing will be performed within 7 days prior to treatment.
  14. Clinical performance status of ECOG 0 - 2 at the time of chemotherapy infusion. (Turnstile II - Chemotherapy/Cell Infusion-Inclusion Criteria).
  15. Absolute neutrophil count greater than or equal to 750/mm3. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  16. Platelet count greater than or equal to 75,000/mm3. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  17. Hemoglobin greater than or equal to 8.0 g/dl. (Turnstile II - Chemotherapy/Cell Infusion).
  18. Serum ALT less than three times the upper limit of normal. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).
  19. Serum creatinine less than or equal to 1.6 mg/dl. (Turnstile II - Chemotherapy/Cell Infusion-Inclusion Criteria).
  20. 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).
  21. Patients in Cohort A will be randomized to receive either TIL alone or TIL plus Dendritic cells.
  22. 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).
  23. Pulmonary function tests (FEV1>65% or FVC>65%of predicted) within 6 months of lymphodepletion. (Turnstile II - Chemotherapy/Cell Infusion - Inclusion Criteria).
  24. MRI/CT of the brain within 42 days of lymphodepletion. CT scan of chest/abdomen/pelvis or PET/CT within 30 days of lymphodepletion. Exception: Patients randomized to receive dendritic cells may have an MRI of the brain within 30 days of lymphodepletion. (Turnstile II-Chemotherapy/Cell Infusion-Inclusion Criteria)
  25. Patients must be receiving a B-RAF inhibitor and failed to achieve PR or CR or have progressive disease in response to B-RAF treatment (Cohort C).

Exclusion Criteria:

  1. Has had prior systemic cancer cytotoxic chemotherapy within the past four weeks at the time of the start of the lymphodepletion regimen.
  2. Has had prior B-RAF or MEK targeted therapy within 7 days prior to the start of the lymphodepletion regimen (Cohort A and Cohort B).
  3. Is not receiving B-RAF treatment (Cohort C) (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  4. Achieves PR or CR in response to B-RAF treatment (Cohort C).
  5. Women who are pregnant or nursing will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  6. 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)
  7. Any form of primary or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (> 500/mm3), white blood cell count (WBC) (> 3,000/mm3) or absence of opportunistic infections. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  8. 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. Exception: Patients on physiologic dose of steroid (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)
  9. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Prometheus Laboratories
Key Biologics, LLC
Investigators
Principal Investigator: Patrick Hwu, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided by M.D. Anderson Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00338377     History of Changes
Other Study ID Numbers: 2004-0069, NCI-2012-01368
Study First Received: February 10, 2006
Last Updated: June 30, 2014
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

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

ClinicalTrials.gov processed this record on August 26, 2014