Lymphocyte Re-infusion During Immune Suppression to Treat Metastatic Melanoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00001832
• Collaborator: (none)
• Enrollment: 170
• Location: 1
• Arms: 15
• Duration (Months): 129
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma; Neoplasm Metastasis	Drug: gp100:209-217 (210M); Drug: Montanide ISA-51; Drug: IL-2; Drug: MART-1:26-35(27L); Biological: Abl cells; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: GCSF (Growth colony stimulating factor); Procedure: Apheresis	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 170 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Patients With Metastatic Melanoma Using Cloned Lymphocytes Following the Administration of a Non-Myeloablative But Lymphocyte Depleting Regimen
• Study Start Date: Aug 1, 1999
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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.	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	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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: Cytoxan
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	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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: Cytoxan
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	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 Names: Interleukin-2 ; 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: Cytoxan
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	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 Names: Interleukin-2 ; 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: Cytoxan
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	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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: 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 Names: Filgrastim
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	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 Names: Interleukin-2 ; 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: 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 Names: Filgrastim
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	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 Names: Interleukin-2 ; 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: 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 Names: Filgrastim
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.	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 Names: IFA ; 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 Names: 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: 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 Names: Filgrastim
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	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 Names: Interleukin-2 ; 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: Cytoxan
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	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: 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 Names: Interleukin-2 ; 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: Cytoxan
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	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 Names: 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 Names: 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: Cytoxan
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	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 Names: Interleukin-2 ; 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: 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 Names: Filgrastim
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	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 Names: 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 Names: 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: 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 Names: Filgrastim
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	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 Names: Interleukin-2 ; 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 Names: Fludara ; Drug: Cyclophosphamide; 2x30 mg/kg, 2x60 mg/kg intravenous; Other Names: 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 Names: Filgrastim

Outcome Measures

Primary Outcome Measures

1. Clinical Response [Every three to four weeks after the treatment, for up to 5 years.]

   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.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [10.5 months]

   Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Institute (NCI)	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Steven Rosenberg, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9.

• Responsible Party: Steven Rosenberg, Dr. Steven Rosenberg, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00001832
• Other Study ID Numbers: 990158; 99-C-0158; NCT00019942
• First Posted: Nov 4, 1999
• Last Update Posted: Dec 21, 2012
• Last Verified: Dec 1, 2012

• Keywords provided by Steven Rosenberg, Dr. Steven Rosenberg, National Institutes of Health Clinical Center (CC): Immunotherapy; Adoptive Transfer; IL-2; Toxicity; Clinical Response; Breast Cancer
• Additional relevant MeSH terms: Melanoma; Neoplasm Metastasis; Cyclophosphamide; Fludarabine; Interleukin-2; Monatide (IMS 3015)

Study Results

Participant Flow

Arm/Group Title	Abl Cells in Culture	Abl Cells IV + Cyclophosphamide 30 mg/kg	Abl Cells IV + Cyclophosphamide 60 mg/kg	Abl Cells IV+Low Dose IV IL-2 (Initial)	Abl Cells IV+High Dose IV IL-2 (Initial)	Abl Cells IV + MTD IL-2	Abl Cells IA + MTD (Prior Cells IV on 6)	Abl Cells IA + MTD IL-2	Abl Cells IA+MTD IL-2 (MART-1 Reactive)	Abl Cells IV + MTD IL-2 no GCSF	Abl Cells IV+MTD IL-2 no GCSF(gp100 Reactive)	Abl Cells IV+MTD IL-2 no GCSF (MART-1reactive)	Abl Cells IV + SQ IL-2 With GCSF	Abl Cells IV + SQ IL-2 With GCSF (MART-1 Reactive)	Abl Cells IV + SQ IL-2 With GCSF (no Reactivity)
Arm/Group Description	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. All patients were enrolled on Arm 0 and their cells were then sent to the lab. If the lab was able to manufacture the cell product then the patient was enrolled on one of the treatment arms.	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x30mg/kg + Cells intravenous (IV)	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV)	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)	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)	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)	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)	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)	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	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 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 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	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 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	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
Period Title: Apheresis Period
STARTED	170	0	0	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	110	0	0	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	60	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Apheresis Period
STARTED	0	3	3	3	6	51	4	7	8	6	1	7	6	3	2
COMPLETED	0	3	3	3	6	50	4	6	8	6	1	7	6	3	2
NOT COMPLETED	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Cells IV + Cyclophosphamide 30mg/kg	Cells IV + Cyclophosphamide 60mg/kg	Cells IV + Low-Dose IV IL-2 (Initial)	Cells IV + High-Dose IV IL-2 (Initial)	Cells IV + MTD IL-2	Cells IA + MTD IL-2 (Prior Cells IV on 6)	Cells IA + MTD IL-2	Cells IA + MTD IL-2 (MART-1 Reactive)	Cells IV + MTD IL-2 no GCSF	Cells IV + MTD IL-2 no GCSF (gp100 Reactive)	Cells IV + MTD IL-2 no GCSF (MART-1 Reactive)	Cells IV + SQ IL-2 w/GCSF	Cells IV + SQ IL-2 w/GCSF (MART-1 Reactive)	Cells IV + SQ IL-2 w/GCSF (no Reactivity)	Total
Arm/Group Description	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x30mg/kg + Cells IV	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IV	Phase 1 IL-2 Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IV + IV IL-2 (72,000 IU/kg q8h for a maximum of 15 doses)	Phase 1 IL-2 Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IV + IV IL-2 (720,000 IU/kg q8h for a maximum of 12 doses)	Phase 2 Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IV + IV IL-2 (720,000 IU/kg q8h for a maximum of 12 doses) + G-CSF (to shorten time to neutrophil recovery)	Phase 2 Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IA + IV IL-2 (720,000 IU/kg q8h for a maximum of 12 doses) Prior Cells IV + G-CSF	Phase 2 Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IA + IV IL-2 (720,000 IU/kg q8h for a maximum of 12 doses) + G-CSF	Phase 2 Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IA + IV IL-2 (720,000 IU/kg q8h for a maximum of 12 doses) + G-CSF + MART-1:26-35(27L) Peptide 1mg/day (5-8 days) in patients with MART-1 reactive cells	Phase 2 Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IV + IV IL-2 (720,000 IU/kg q8h for a maximum of 12 doses) without G-CSF (to determine if G-CSF has harmful effects when adoptively transferring lymphocytes following a nonmyeloablative chemotherapy regimen)	Phase 2 Fludarabine 5x25mg/m2 + 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	Phase 2 Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells IV + IV 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	Phase 2 Fludarabine 5x25mg/m2 + 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 (to shorten time to neutrophil recovery), reactivity not specified	Phase 2 Fludarabine 5x25mg/m2 + 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	Phase 2 Fludarabine 5x25mg/m2 + 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 in patients with no reactivity	Total of all reporting groups
Overall Participants	3	3	3	6	51	4	7	8	6	1	7	6	3	2	110
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.9%
Between 18 and 65 years	3 100%	3 100%	3 100%	5 83.3%	51 100%	4 100%	7 100%	8 100%	6 100%	1 100%	7 100%	6 100%	3 100%	1 50%	108 98.2%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%	1 0.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.3 (9.3)	52.3 (4.5)	42.3 (13.3)	37.8 (14.7)	41.9 (12.7)	38.0 (14.3)	39.7 (11.1)	41.8 (11.6)	49.0 (10.3)	62.0	40.7 (9.9)	44.2 (11.2)	37.7 (7.1)	58.5 (10.6)	45.0 (11.4)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 33.3%	1 33.3%	2 33.3%	22 43.1%	0 0%	2 28.6%	5 62.5%	1 16.7%	1 100%	1 14.3%	1 16.7%	0 0%	0 0%	38 34.5%
Male	2 66.7%	2 66.7%	2 66.7%	4 66.7%	29 56.9%	4 100%	5 71.4%	3 37.5%	5 83.3%	0 0%	6 85.7%	5 83.3%	3 100%	2 100%	72 65.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	3 5.9%	0 0%	0 0%	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	4 3.6%
Not Hispanic or Latino	3 100%	3 100%	3 100%	6 100%	48 94.1%	4 100%	7 100%	8 100%	6 100%	1 100%	6 85.7%	6 100%	3 100%	2 100%	106 96.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	1 2%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.9%
White	3 100%	3 100%	3 100%	6 100%	50 98%	4 100%	7 100%	8 100%	6 100%	1 100%	7 100%	6 100%	3 100%	2 100%	109 99.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	3 100%	6 100%	51 100%	4 100%	7 100%	8 100%	6 100%	1 100%	7 100%	6 100%	3 100%	2 100%	110 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Response
Description	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.
Time Frame	Every three to four weeks after the treatment, for up to 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abl Cells IV + Cyclophosphamide 30 mg/kg	Abl Cells IV + Cyclophosphamide 60 mg/kg	Abl Cells IV+Low Dose IV IL-2 (Initial)	Abl Cells IV+High Dose IV IL-2 (Initial)	Abl Cells IV + MTD IL-2	Abl Cells IA + MTD (Prior Cells IV on 6)	Abl Cells IA + MTD IL-2	Abl Cells IA+MTD IL-2 (MART-1 Reactive)	Abl Cells IV + MTD IL-2 no GCSF	Abl Cells IV+MTD IL-2 no GCSF(gp100 Reactive)	Abl Cells IV+MTD IL-2 no GCSF (MART-1reactive)	Abl Cells IV + SQ IL-2 With GCSF	Abl Cells IV + SQ IL-2 With GCSF (MART-1 Reactive)	Abl Cells IV + SQ IL-2 With GCSF (no Reactivity)
Arm/Group Description	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x30mg/kg + Cells intravenous (IV)	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV)	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)	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)	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)	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)	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)	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	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 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 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	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 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	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
Measure Participants	3	3	3	6	50	4	6	8	6	1	7	6	3	2
Complete Response	0 0%	0 0%	0 0%	0 0%	3 5.9%	0 0%	1 14.3%	1 12.5%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%
Partial Response	0 0%	0 0%	0 0%	0 0%	14 27.5%	0 0%	0 0%	1 12.5%	1 16.7%	0 0%	2 28.6%	3 50%	1 33.3%	0 0%
Minor Response	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 100%	0 0%	0 0%	0 0%	0 0%
Progressive Disease	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Mixed Response	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 12.5%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
No Response	3 100%	3 100%	3 100%	6 100%	32 62.7%	4 100%	5 71.4%	5 62.5%	4 66.7%	0 0%	5 71.4%	3 50%	2 66.7%	2 100%
Stable Disease	0 0%	0 0%	0 0%	0 0%	1 2%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Time Frame	10.5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abl Cells IV + Cyclophosphamide 30 mg/kg	Abl Cells IV + Cyclophosphamide 60 mg/kg	Abl Cells IV+Low Dose IV IL-2 (Initial)	Abl Cells IV+High Dose IV IL-2 (Initial)	Abl Cells IV + MTD IL-2	Abl Cells IA + MTD (Prior Cells IV on 6)	Abl Cells IA + MTD IL-2	Abl Cells IA+MTD IL-2 (MART-1 Reactive)	Abl Cells IV + MTD IL-2 no GCSF	Abl Cells IV+MTD IL-2 no GCSF(gp100 Reactive)	Abl Cells IV+MTD IL-2 no GCSF (MART-1reactive)	Abl Cells IV + SQ IL-2 With GCSF	Abl Cells IV + SQ IL-2 With GCSF (MART-1 Reactive)	Abl Cells IV + SQ IL-2 With GCSF (no Reactivity)
Arm/Group Description	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x30mg/kg + Cells intravenous (IV)	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV)	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)	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)	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)	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)	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)	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	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 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 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	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 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	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
Measure Participants	3	3	3	6	51	4	7	8	6	1	7	6	3	2
Number [Participants]	3 100%	3 100%	3 100%	6 100%	50 98%	4 100%	7 100%	8 100%	6 100%	1 100%	7 100%	6 100%	3 100%	2 100%

Adverse Events

Arm/Group Title	Abl Cells IV + Cyclophosphamide 30 mg/kg		Abl Cells IV + Cyclophosphamide 60 mg/kg		Abl Cells IV+Low Dose IV IL-2 (Initial)		Abl Cells IV+High Dose IV IL-2 (Initial)		Abl Cells IV + MTD IL-2		Abl Cells IA + MTD (Prior Cells IV on 6)		Abl Cells IA + MTD IL-2		Abl Cells IA+MTD IL-2 (MART-1 Reactive)		Abl Cells IV + MTD IL-2 no GCSF		Abl Cells IV+MTD IL-2 no GCSF(gp100 Reactive)		Abl Cells IV+MTD IL-2 no GCSF (MART-1reactive)		Abl Cells IV + SQ IL-2 With GCSF		Abl Cells IV + SQ IL-2 With GCSF (MART-1 Reactive)		Abl Cells IV + SQ IL-2 With GCSF (no Reactivity)
Arm/Group Description	Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m^2 + Cyclophosphamide 2x30mg/kg + Cells intravenous (IV)		Phase 1 Cyclophosphamide Dose Escalation: Fludarabine 5x25mg/m2 + Cyclophosphamide 2x60mg/kg + Cells intravenous (IV)		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)		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)		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)		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)		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)		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		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 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 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		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) + granulocyte colony stimulating factor (G-CSF) (to shorten time to neutrophil recovery), reactivity not specified		Abl Cells intravenous (IV) + subcutaneous (SQ) interleukin-2 (IL-2) with granulocyte 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		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
All Cause Mortality
	Abl Cells IV + Cyclophosphamide 30 mg/kg		Abl Cells IV + Cyclophosphamide 60 mg/kg		Abl Cells IV+Low Dose IV IL-2 (Initial)		Abl Cells IV+High Dose IV IL-2 (Initial)		Abl Cells IV + MTD IL-2		Abl Cells IA + MTD (Prior Cells IV on 6)		Abl Cells IA + MTD IL-2		Abl Cells IA+MTD IL-2 (MART-1 Reactive)		Abl Cells IV + MTD IL-2 no GCSF		Abl Cells IV+MTD IL-2 no GCSF(gp100 Reactive)		Abl Cells IV+MTD IL-2 no GCSF (MART-1reactive)		Abl Cells IV + SQ IL-2 With GCSF		Abl Cells IV + SQ IL-2 With GCSF (MART-1 Reactive)		Abl Cells IV + SQ IL-2 With GCSF (no Reactivity)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Abl Cells IV + Cyclophosphamide 30 mg/kg		Abl Cells IV + Cyclophosphamide 60 mg/kg		Abl Cells IV+Low Dose IV IL-2 (Initial)		Abl Cells IV+High Dose IV IL-2 (Initial)		Abl Cells IV + MTD IL-2		Abl Cells IA + MTD (Prior Cells IV on 6)		Abl Cells IA + MTD IL-2		Abl Cells IA+MTD IL-2 (MART-1 Reactive)		Abl Cells IV + MTD IL-2 no GCSF		Abl Cells IV+MTD IL-2 no GCSF(gp100 Reactive)		Abl Cells IV+MTD IL-2 no GCSF (MART-1reactive)		Abl Cells IV + SQ IL-2 With GCSF		Abl Cells IV + SQ IL-2 With GCSF (MART-1 Reactive)		Abl Cells IV + SQ IL-2 With GCSF (no Reactivity)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		9/51 (17.6%)		0/4 (0%)		2/7 (28.6%)		1/8 (12.5%)		0/6 (0%)		0/1 (0%)		0/7 (0%)		0/6 (0%)		1/3 (33.3%)		1/2 (50%)
Blood and lymphatic system disorders
Lymphocyte count decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Neutrophil count decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Thrombotic microangiopathy	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Disseminated intravascular coagulation	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Cardiac disorders
Sinus tachycardia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Hypotension	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
left ventricular dysfunction	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Eye disorders
Vision blurred	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
General disorders
General symptom	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Infections and infestations
Infection (documented clinically or microbiologically)	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Infection/Febrile neutropenia (infection without neutropenia)	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Infection (documented clinically or microbiologically)	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Metabolism and nutrition disorders
Creatinine increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Nervous system disorders
Confusion	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Hallucinations	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Leukoencephalopathy	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Neurological disorder NOS	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
peripheral sensory neuropathy	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Pneumonitis	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Renal failure	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Dyspnea	0/0 (NaN)	0	0/0 (NaN)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Vascular disorders
Thrombosis	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Peripheral ischemia	0/0 (NaN)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Abl Cells IV + Cyclophosphamide 30 mg/kg		Abl Cells IV + Cyclophosphamide 60 mg/kg		Abl Cells IV+Low Dose IV IL-2 (Initial)		Abl Cells IV+High Dose IV IL-2 (Initial)		Abl Cells IV + MTD IL-2		Abl Cells IA + MTD (Prior Cells IV on 6)		Abl Cells IA + MTD IL-2		Abl Cells IA+MTD IL-2 (MART-1 Reactive)		Abl Cells IV + MTD IL-2 no GCSF		Abl Cells IV+MTD IL-2 no GCSF(gp100 Reactive)		Abl Cells IV+MTD IL-2 no GCSF (MART-1reactive)		Abl Cells IV + SQ IL-2 With GCSF		Abl Cells IV + SQ IL-2 With GCSF (MART-1 Reactive)		Abl Cells IV + SQ IL-2 With GCSF (no Reactivity)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		6/6 (100%)		50/51 (98%)		4/4 (100%)		7/7 (100%)		8/8 (100%)		6/6 (100%)		1/1 (100%)		7/7 (100%)		6/6 (100%)		3/3 (100%)		2/2 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/3 (33.3%)	1	2/3 (66.7%)	4	3/3 (100%)	4	4/6 (66.7%)	5	37/51 (72.5%)	50	3/4 (75%)	3	5/7 (71.4%)	8	6/8 (75%)	9	2/6 (33.3%)	3	1/1 (100%)	1	5/7 (71.4%)	10	3/6 (50%)	3	1/3 (33.3%)	1	1/2 (50%)	1
Leukocyte count decreased	3/3 (100%)	3	3/3 (100%)	3	3/3 (100%)	4	6/6 (100%)	7	50/51 (98%)	66	4/4 (100%)	4	5/7 (71.4%)	8	7/8 (87.5%)	12	6/6 (100%)	9	1/1 (100%)	1	7/7 (100%)	9	6/6 (100%)	7	3/3 (100%)	3	2/2 (100%)	2
Lymphocyte count decreased	3/3 (100%)	4	3/3 (100%)	4	3/3 (100%)	6	5/6 (83.3%)	9	50/51 (98%)	80	3/4 (75%)	4	6/7 (85.7%)	12	8/8 (100%)	19	5/6 (83.3%)	12	1/1 (100%)	1	7/7 (100%)	13	6/6 (100%)	10	3/3 (100%)	3	2/2 (100%)	4
Neutrophil count decreased	3/3 (100%)	3	3/3 (100%)	3	3/3 (100%)	3	6/6 (100%)	7	50/51 (98%)	70	4/4 (100%)	4	5/7 (71.4%)	10	7/8 (87.5%)	11	6/6 (100%)	8	1/1 (100%)	1	7/7 (100%)	8	6/6 (100%)	8	3/3 (100%)	3	2/2 (100%)	2
Activated partial thromboplastin time prolonged	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	9/51 (17.6%)	11	1/4 (25%)	1	2/7 (28.6%)	2	4/8 (50%)	4	0/6 (0%)	0	0/1 (0%)	0	3/7 (42.9%)	5	1/6 (16.7%)	1	1/3 (33.3%)	1	0/2 (0%)	0
Platelet count decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	23/51 (45.1%)	27	1/4 (25%)	1	6/7 (85.7%)	9	5/8 (62.5%)	5	2/6 (33.3%)	3	0/1 (0%)	0	4/7 (57.1%)	5	6/6 (100%)	6	1/3 (33.3%)	1	2/2 (100%)	2
INR increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	3/51 (5.9%)	3	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	1/6 (16.7%)	1	0/1 (0%)	0	0/7 (0%)	0	4/6 (66.7%)	4	0/3 (0%)	0	0/2 (0%)	0
Thrombotic microangiopathy	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Petechiae	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/2 (0%)	0
Cardiac disorders
Sinus tachycardia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	3/51 (5.9%)	3	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	2	0/3 (0%)	0	0/2 (0%)	0
Hypotension	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	3/51 (5.9%)	3	0/4 (0%)	0	1/7 (14.3%)	1	2/8 (25%)	2	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/3 (66.7%)	2	0/2 (0%)	0
Hypertension	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/2 (0%)	0
Ear and labyrinth disorders
Hearing loss	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Eye disorders
Vision blurred	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/2 (0%)	0
Gastrointestinal disorders
Anorexia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Constipation	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Diarrhea	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	4/51 (7.8%)	6	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/2 (50%)	1
Nausea	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	5/51 (9.8%)	6	0/4 (0%)	0	2/7 (28.6%)	2	2/8 (25%)	2	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	2	0/3 (0%)	0	0/2 (0%)	0
Vomiting	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	5/51 (9.8%)	5	0/4 (0%)	0	0/7 (0%)	0	3/8 (37.5%)	3	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	2	0/3 (0%)	0	0/2 (0%)	0
Rectal pain	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Rectal bleeding/hematochezia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Dyspepsia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
General disorders
Fatigue	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	5/51 (9.8%)	5	0/4 (0%)	0	3/7 (42.9%)	3	2/8 (25%)	2	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	1/2 (50%)	2
Fever	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/51 (3.9%)	2	0/4 (0%)	0	2/7 (28.6%)	3	1/8 (12.5%)	2	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	4/6 (66.7%)	5	0/3 (0%)	0	0/2 (0%)	0
Pain	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Chills	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	2/7 (28.6%)	2	1/8 (12.5%)	2	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/2 (0%)	0
Weight loss	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	1/6 (16.7%)	1	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Insomnia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Weight gain	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/2 (0%)	0
General symptom	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/6 (16.7%)	1	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/2 (0%)	0
Immune system disorders
Autoimmune disorder	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/2 (0%)	0
Infections and infestations
Febrile Neutropenia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	17/51 (33.3%)	18	0/4 (0%)	0	2/7 (28.6%)	2	2/8 (25%)	2	3/6 (50%)	3	0/1 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	2/3 (66.7%)	2	1/2 (50%)	1
Infection (documented clinically or microbiologically)	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	2/8 (25%)	2	1/6 (16.7%)	1	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Wound infection	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Catheter-related infection	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Metabolism and nutrition disorders
Serum albumin decreased	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	16/51 (31.4%)	19	1/4 (25%)	1	3/7 (42.9%)	4	6/8 (75%)	6	3/6 (50%)	3	0/1 (0%)	0	3/7 (42.9%)	7	2/6 (33.3%)	2	2/3 (66.7%)	2	1/2 (50%)	1
Bilirubin increased	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	2/6 (33.3%)	2	16/51 (31.4%)	17	1/4 (25%)	1	2/7 (28.6%)	4	4/8 (50%)	4	2/6 (33.3%)	3	0/1 (0%)	0	2/7 (28.6%)	2	0/6 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Serum calcium decreased	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	2/6 (33.3%)	3	11/51 (21.6%)	12	0/4 (0%)	0	4/7 (57.1%)	4	4/8 (50%)	4	1/6 (16.7%)	2	0/1 (0%)	0	2/7 (28.6%)	5	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Serum magnesium decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Serum phosphate decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	20/51 (39.2%)	26	1/4 (25%)	1	2/7 (28.6%)	6	4/8 (50%)	6	0/6 (0%)	0	0/1 (0%)	0	5/7 (71.4%)	8	0/6 (0%)	0	1/3 (33.3%)	1	1/2 (50%)	1
Alkaline phosphatase increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Alanine aminotransferase increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Aspartate aminotransferase increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Creatinine increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	9/51 (17.6%)	9	0/4 (0%)	0	2/7 (28.6%)	2	1/8 (12.5%)	2	2/6 (33.3%)	3	0/1 (0%)	0	1/7 (14.3%)	1	2/6 (33.3%)	2	0/3 (0%)	0	1/2 (50%)	1
Lipase increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Serum potassium increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	2/7 (28.6%)	2	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Serum potassium decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	11/51 (21.6%)	11	0/4 (0%)	0	0/7 (0%)	0	2/8 (25%)	5	0/6 (0%)	0	0/1 (0%)	0	2/7 (28.6%)	3	1/6 (16.7%)	1	0/3 (0%)	0	0/2 (0%)	0
Serum sodium decreased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	8/51 (15.7%)	10	1/4 (25%)	1	2/7 (28.6%)	2	1/8 (12.5%)	1	1/6 (16.7%)	1	0/1 (0%)	0	2/7 (28.6%)	2	0/6 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Serum triglycerides increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/3 (66.7%)	2	0/2 (0%)	0
Blood uric acid increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	10/51 (19.6%)	15	0/4 (0%)	0	1/7 (14.3%)	7	3/8 (37.5%)	5	2/6 (33.3%)	4	0/1 (0%)	0	1/7 (14.3%)	2	1/6 (16.7%)	1	0/3 (0%)	0	1/2 (50%)	1
Serum magnesium increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	4/51 (7.8%)	4	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	1/6 (16.7%)	1	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Serum calcium increased	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	2/7 (28.6%)	3	2/8 (25%)	2	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Nervous system disorders
Confusion	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	5/51 (9.8%)	5	0/4 (0%)	0	0/7 (0%)	0	3/8 (37.5%)	3	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	1/2 (50%)	1
Anxiety	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Neurological disorder NOS	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0
Headache	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Somnolence/depressed level of consciousness	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	2/7 (28.6%)	2	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Depression	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Syncope	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Hallucinations	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/6 (16.7%)	1	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	1/2 (50%)	1
Psychosis	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/2 (50%)	1
Renal and urinary disorders
Low urine output	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	1/2 (50%)	1
Reproductive system and breast disorders
Irregular menstruation	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Abdominal pain	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hemorrhage nasal	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Cough	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/51 (3.9%)	2	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Dyspnea	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	8/51 (15.7%)	9	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Hypoxia	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/51 (3.9%)	2	0/4 (0%)	0	1/7 (14.3%)	2	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Respiratory disorder	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Pigmentation changes (e.g., vitiligo)	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/51 (2%)	1	0/4 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Rash desquamating	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	4/51 (7.8%)	4	0/4 (0%)	0	2/7 (28.6%)	2	1/8 (12.5%)	1	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1	0/2 (0%)	0
Injection site reaction	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	0/2 (0%)	0
Vascular disorders
Capillary leak syndrome	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/51 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/6 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	2	1/3 (33.3%)	1	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.