Expired Study
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Bethesda, Maryland 20892


Purpose:

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.


Study summary:

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.


Criteria:

- 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.


Study is Available At:


Original ID:

990158


NCT ID:

NCT00001832


Secondary ID:

99-C-0158


Study Acronym:


Brief Title:

Lymphocyte Re-infusion During Immune Suppression to Treat Metastatic Melanoma


Official Title:

Treatment of Patients With Metastatic Melanoma Using Cloned Lymphocytes Following the Administration of a Non-Myeloablative But Lymphocyte Depleting Regimen


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

7 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institutes of Health Clinical Center (CC)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Endpoint Classificati


Number of Arms:

15


Number of Groups:

0


Total Enrollment:

170


Enrollment Type:

Actual


Overall Contact Information

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

Study Dates

Start Date:August 1999
Completion Date:May 2010
Completion Type:Actual
Primary Completion Date:May 2010
Primary Completion Type:Actual
Verification Date:December 2012
Last Changed Date:December 19, 2012
First Received Date:November 3, 1999
First Results Date:November 7, 2012

Study Outcomes

Outcome Type:Primary Outcome
Measure:Clinical Response
Time Frame:Every three to four weeks after the treatment, for up to 5 years.
Safety Issues:False
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 l
Outcome Type:Secondary Outcome
Measure:Number of Participants With Adverse Events
Time Frame:10.5 months
Safety Issues:True
Description:Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Study Interventions

Intervention Type:Drug
Name:gp100:209-217 (210M)
Description: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 t
Arm Name:Abl Cells IV+MTD IL-2 no GCSF
Intervention Type:Drug
Name:Montanide ISA-51
Description: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.
Arm Name:Abl Cells IA+MTD IL-2 (MART-1 reactive)
Other Name:IFA
Intervention Type:Drug
Name:IL-2
Description: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.
Arm Name:Abl Cells IV+Low Dose IV IL-2 (Initial)
Other Name:Interleukin-2
Intervention Type:Drug
Name:MART-1:26-35(27L)
Description: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.
Arm Name:Abl Cells IA+MTD IL-2 (MART-1 reactive)
Other Name:melanoma-associated antigen recognized by T cells
Intervention Type:Biological
Name:Abl cells
Description: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
Arm Name:Abl Cells IV + Cyclophosphamide 30 mg/kg
Intervention Type:Drug
Name:Fludarabine
Description:5x25 mg/m^2 intravenous
Arm Name:Abl Cells IV + Cyclophosphamide 30 mg/kg
Other Name:Fludara
Intervention Type:Drug
Name:Cyclophosphamide
Description:2x30 mg/kg, 2x60 mg/kg intravenous
Arm Name:Abl Cells IV + Cyclophosphamide 30 mg/kg
Other Name:Cytoxan
Intervention Type:Biological
Name:GCSF (Growth colony stimulating factor)
Description: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.
Arm Name:Abl Cells IV + MTD IL-2
Other Name:Filgrastim
Intervention Type:Procedure
Name:Apheresis
Arm Name:Abl Cells in culture

Study Arms

Study Arm Type:Experimental
Arm Name:Abl Cells in culture
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.The patients underwent an apheresis and/or an excision of their tumor. They didn't receive any drugs.
Study Arm Type:Experimental
Arm Name:Abl Cells IV + Cyclophosphamide 30 mg/kg
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV + Cyclophosphamide 60 mg/kg
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV+Low Dose IV IL-2 (Initial)
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV+High Dose IV IL-2 (Initial)
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV + MTD IL-2
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IA + MTD (prior cells IV on 6)
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IA + MTD IL-2
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IA+MTD IL-2 (MART-1 reactive)
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV + MTD IL-2 no GCSF
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV+MTD IL-2 no GCSF
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV+MTD IL-2
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV + SQ IL-2 with GCSF
Description: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
Study Arm Type:Experimental
Arm Name:Abl Cells IV + SQ
Description: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, rep
Study Arm Type:Experimental
Arm Name:Abl Cells IV + SQ IL-2 with GCSF (no reactivity)
Description: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

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation: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.
PMID:8170938

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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