Lymphocyte Re-infusion During Immune Suppression to Treat Metastatic Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Steven Rosenberg, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001832
First received: November 3, 1999
Last updated: December 19, 2012
Last verified: December 2012

November 3, 1999
December 19, 2012
August 1999
May 2010   (final data collection date for primary outcome measure)
Clinical Response [ Time Frame: Every three to four weeks after the treatment, for up to 5 years. ] [ Designated as safety issue: No ]
Complete response (CR) is defined as the disappearance of all clinical evidence of disease. Partial response (PR) is a 50% or greater decrease in the sum of the products of perpendicular diameters of all measurable lesions for at least one month. No new lesions may appear, and none may increase. Minor response (MR) is a 25-49% decrease in the sum of the products of the perpendicular diameters of all measurable lesions. Appearance of new lesions following a PR or CR are considered relapses. Patients with progressive disease (PD) and no evidence of stable disease will be taken off study after receiving IL-2.
Not Provided
Complete list of historical versions of study NCT00001832 on ClinicalTrials.gov Archive Site
Number of Participants With Adverse Events [ Time Frame: 10.5 months ] [ Designated as safety issue: Yes ]
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Not Provided
Not Provided
Not Provided
 
Lymphocyte Re-infusion During Immune Suppression to Treat Metastatic Melanoma
Treatment of Patients With Metastatic Melanoma Using Cloned Lymphocytes Following the Administration of a Non-Myeloablative But Lymphocyte Depleting Regimen

This experiment will test the safety and effectiveness of a treatment for melanoma in which certain lymphocytes (a type of white blood cell) are taken from the patient, grown in the laboratory, and returned after the patient's immune system has been weakened with immune-suppressing drugs. Some patients will also receive interleukin-2 (IL-2), a drug that may enhance the activity of the re-infused lymphocytes.

Patients with metastatic melanoma (melanoma whose tumor has spread) who have been treated unsuccessfully with gp100 vaccination may participate in this study. They will undergo apheresis or a tumor biopsy, or both, to collect lymphocytes. In apheresis, whole blood is drawn through a needle in the arm. A machine separates the blood components and removes the white cells. The rest of the blood is returned to the donor through a needle in the other arm. A biopsy is a surgical procedure to remove a small piece of tumor tissue.

Several weeks before the lymphocytes are collected, patients will receive injections of growth colony stimulating factor (G-CSF) every day for five days. This drug stimulates white cell production, permitting as many cells as possible to be obtained during collection. The lymphocytes will then be grown in larger numbers in the laboratory.

Seven days before the cells are re-infused, the patient is admitted to the hospital and a catheter (small tube) is placed in a large vein in the chest or neck. Two drugs, cyclophosphamide and fludarabine, are given through the tube. These drugs suppress the immune system so that it will not interfere with the work of the reinfused lymphocytes. The lymphocytes are then injected through the catheter over a 30-minute period. After the infusion, patients who receive IL-2 will be given the drug in a high dose over a 15-minute period every eight hours for up to five days. Patients whose condition does not permit high-dose IL-2, such as those with a heart condition or lung problem, may receive a low-dose regimen, with the drug given as a shot under the skin of the thigh or abdomen for five days followed by a 2-day break, continuing for a total of six weeks. These patients receive a higher dose the first week and then half that dose the next five weeks.

Blood and tissue samples will be taken before and during the study to evaluate the size of the tumor and assess treatment. If, 3-5 weeks after therapy is completed, the patient's tumor has stabilized or shrunk, the entire treatment, except for chemotherapy, may be repeated two more times.

Patients with metastatic melanoma who are human immunodeficiency virus (HIV) and Hepatitis B negative and who have previously progressed after receiving standard therapy will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine and then will be treated by the adoptive transfer of lymphocytes reactive with shared antigens on their tumors. This study will evaluate the toxicity, immunologic effects and potential therapeutic role of this treatment.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Melanoma
  • Neoplasm Metastasis
  • Drug: gp100:209-217 (210M)

    gp100 = gp100:209‑217(210M) peptide - 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus gp100:209‑217(210M) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.

    MART-1 = MART‑1:26‑35(27L) peptide- 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus MART‑1:26‑35(27L) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.

  • Drug: Montanide ISA-51
    MART-1 = MART‑1:26‑35(27L) peptide- 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus MART‑1:26‑35(27L) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.
    Other Name: IFA
  • Drug: IL-2

    125,000 IU/kg dose intravenous for 5 days for 6 weeks with 2 days rest per week.

    720,000 IU/kg intravenous every 8 hours for a maximum of 12 doses.

    Other Name: Interleukin-2
  • Drug: MART-1:26-35(27L)
    MART-1 = MART‑1:26‑35(27L) peptide- 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus MART‑1:26‑35(27L) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.
    Other Name: melanoma-associated antigen recognized by T cells
  • Biological: Abl cells
    Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days Abl cells IA = Lymphocytes 10^9‑10^11 IA over 30 minutes on day 0, repeated in 14 to 21 days
  • Drug: Fludarabine
    5x25 mg/m^2 intravenous
    Other Name: Fludara
  • Drug: Cyclophosphamide
    2x30 mg/kg, 2x60 mg/kg intravenous
    Other Name: Cytoxan
  • Biological: GCSF (Growth colony stimulating factor)
    Beginning on day 1 or 2, GCSF will be administered subcutaneously at a dose of 5mcg/kg/day (not to exceed 300 mcg/day. Filgrastim administration will continue daily until neutrophil count > 1.0 x10^9/L x 3 days or > 5.0 x10^9/L.
    Other Name: Filgrastim
  • Procedure: Apheresis
  • Experimental: Abl Cells in culture

    Peripheral blood mononuclear cells (PBMC) and/or tumor infiltrating lymphocytes (TIL) obtained by apheresis or lesion excision to be cloned and expanded in the lab.The patients underwent an apheresis and/or an excision of their tumor.

    They didn't receive any drugs.

    Intervention: Procedure: Apheresis
  • Experimental: Abl Cells IV + Cyclophosphamide 30 mg/kg
    Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x30mg/kg + Cells intravenous (IV) Abl cells intravenous (IV) = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Abl Cells IV + Cyclophosphamide 60 mg/kg
    Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV) Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Abl Cells IV+Low Dose IV IL-2 (Initial)
    Phase 1 interleukin-2 (IL-2) Dose Escalation: Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV) + IV IL-2 (72,000 IU/kg q8h for a maximum of 15 doses) Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Drug: IL-2
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Abl Cells IV+High Dose IV IL-2 (Initial)
    Phase 1 interleukin-2 (IL-2) Dose Escalation: Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV) + IV IL-2 (720,000 IU/kg q8h for a maximum of 12 doses) Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Drug: IL-2
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Abl Cells IV + MTD IL-2
    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV) + IV interleukin-2 (IL-2) (720,000 IU/kg q8h for a maximum of 12 doses) + growth colony stimulating factor (G-CSF) (to shorten time to neutrophil recovery) Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
    • Biological: GCSF (Growth colony stimulating factor)
  • Experimental: Abl Cells IA + MTD (prior cells IV on 6)
    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intra-arterial (IA) + intravenous (IV) interleukin-2 (IL-2) (720,000 IU/kg q8h for a maximum of 12 doses) Prior Cells IV + growth colony stimulating factor (G-CSF) Abl cells IA = Lymphocytes 10^9‑10^11 IA over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Drug: IL-2
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
    • Biological: GCSF (Growth colony stimulating factor)
  • Experimental: Abl Cells IA + MTD IL-2
    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intra-arterial (IA) + intravenous (IV) interleukin-2 (IL-2) (720,000 IU/kg q8h for a maximum of 12 doses) + growth colony stimulating factor (G-CSF) Abl cells IA = Lymphocytes 10^9‑10^11 IA over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Drug: IL-2
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
    • Biological: GCSF (Growth colony stimulating factor)
  • Experimental: Abl Cells IA+MTD IL-2 (MART-1 reactive)
    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intra-arterial (IA) + intravenous (IV) interleukin-2 (IL-2) (720,000 IU/kg q8h for a maximum of 12 doses) + growth colony stimulating factor (G-CSF) + melanoma- associated antigen recognized by T cells (MART-1):26-35(27L) Peptide 1mg/day (5-8 days) in patients with MART-1 reactive cells Abl cells IA = Lymphocytes 10^9‑10^11 IA over 30 minutes on day 0, repeated in 14 to 21 days gp100 = gp100:209‑217(210M) peptide - 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus gp100:209‑217(210M) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.
    Interventions:
    • Drug: Montanide ISA-51
    • Drug: MART-1:26-35(27L)
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
    • Biological: GCSF (Growth colony stimulating factor)
  • Experimental: Abl Cells IV + MTD IL-2 no GCSF
    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV) + IV interleukin-2 (IL-2) (720,000 IU/kg q8h for a maximum of 12 doses) without growth colony stimulating factor (G-CSF) (to determine if G-CSF has harmful effects when adoptively transferring lymphocytes following a nonmyeloablative chemotherapy regimen) Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Drug: IL-2
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Abl Cells IV+MTD IL-2 no GCSF

    Abl Cells intravenous (IV) + maximum tolerated dose (MTD) interleukin-2 (IL-2) no growth colony stimulating factor (GCSF)(gp100 reactive).

    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells IV + IV IL-2 (720,000 IU/kg q8h for a maximum of 12 doses) without G-CSF + gp100:209-217(210M) 1mg/day (2-8 days) in patients with gp100 reactive cells Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days

    Interventions:
    • Drug: gp100:209-217 (210M)
    • Drug: IL-2
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Abl Cells IV+MTD IL-2

    Abl Cells intravenous (IV)+ maximum tolerated dose (MTD) interleukin-2 (IL-2) no growth colony stimulating factor (GCSF) (melanoma-associated antigen recognized by T cells (MART-1)reactive).

    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells IV + IV interleukin-2 (IL-2) (720,000 IU/kg q8h for a maximum of 12 doses) without G-CSF + MART-1:26-35(27L) Peptide 1mg/day (5-8 days) in patients with MART-1 reactive cells Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days

    Interventions:
    • Drug: IL-2
    • Drug: MART-1:26-35(27L)
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Abl Cells IV + SQ IL-2 with GCSF
    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV) + subcutaneous (SQ) interleukin-2 (IL-2) (125,000 IU/kg/dose for 5 days for six weeks with 2 days rest per week) + growth colony stimulating factor (G-CSF) (to shorten time to neutrophil recovery), reactivity not specified Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Drug: IL-2
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
    • Biological: GCSF (Growth colony stimulating factor)
  • Experimental: Abl Cells IV + SQ
    Abl Cells intravenous (IV) + subcutaneous (SQ) interleukin-2 (IL-2) with growth colony stimulating factor (GCSF) (melanoma-associated antigen recognized by T cells (MART-1) reactive) Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells IV + SQ IL-2 (125,000 IU/kg/dose for 5 days for six weeks with 2 days rest per week) + G-CSF + MART-1:26-35(27L) Peptide 1mg/day (5-8 days) in patients with MART-1 reactive cells Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Drug: IL-2
    • Drug: MART-1:26-35(27L)
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
    • Biological: GCSF (Growth colony stimulating factor)
  • Experimental: Abl Cells IV + SQ IL-2 with GCSF (no reactivity)
    Phase 2 Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV) + subcutaneous (SQ) interleukin-2 ( IL-2) (125,000 IU/kg/dose for 5 days for six weeks with 2 days rest per week) + growth colony stimulating factor (G-CSF) in patients with no reactivity Abl cells IV = Lymphocytes 10^9‑10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days
    Interventions:
    • Drug: IL-2
    • Biological: Abl cells
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
    • Biological: GCSF (Growth colony stimulating factor)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
170
May 2010
May 2010   (final data collection date for primary outcome measure)
  • INCLUSION CRITERIA
  • Patients must have evaluable metastatic melanoma that is refractory to standard therapy.
  • Age greater than or equal to 16 years.
  • Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.
  • Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 at entry to the trial and at the time of chemotherapy induction.
  • Absolute neutrophil count greater than 1000/mm^3.
  • Platelet count greater than 100,000/mm^3.
  • Hemoglobin greater than 8.0 g/dl.
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than two times the upper limit of normal.
  • Serum creatinine less than or equal to 1.6 mg/dl.
  • Total bilirubin less than or equal to 1.6 mg/dl, except for patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
  • More than four weeks must have elapsed since any prior therapy at the time the patient receives the preparative regimen.
  • Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
  • Life expectancy of greater than three months.
  • No steroid therapy required.
  • Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Seronegative for hepatitis B antigen.
  • Patients to receive high dose interleukin 2 (IL-2) must have no active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system.
  • Patients who will receive high dose IL-2 as part of the phase I portion of this study or who will be randomized must be eligible to receive high dose IL-2.
  • Any patient receiving IL-2 must sign a durable power of attorney.
Both
7 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00001832
990158, 99-C-0158
Yes
Steven Rosenberg, National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Steven Rosenberg, M.D. National Cancer Institute, National Institutes of Health
National Institutes of Health Clinical Center (CC)
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP