Drosophila-generated CTL

NCT01271907 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 11005211-C-0052
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Recent cancer treatment studies have shown that altering a cancer patient's own white blood cells may help the immune system fight the cancer. In all of these studies, participants donate their own white blood cells through a procedure called leukapheresis, and the cells are altered in the laboratory and given back to the participants. After the cells are given, the patients receive aldesleukin (IL-2) to help the tumor fighting cells stay alive longer. For individuals with metastatic melanoma, pieces of melanoma proteins may be added to the collected white blood cells to help the immune system recognize and attack the cancer cells.
• Researchers are interested in testing a new process in which cells from fruit flies (Drosophila) are used to help the melanoma proteins attach to the white blood cells. The fruit fly cells die off shortly after the proteins are introduced to the white blood cells. Researchers are also interested in determining whether IL-2 treatment is necessary after this new cancer treatment process. Objectives:
• To test the safety and effectiveness of modified white blood cells (Drosophila-generated CTL) as a treatment for metastatic melanoma that has not responded to standard treatments.
• To determine whether IL-2 treatment improves the effectiveness of Drosophila-generated cytolytic T lymphocytes (CTL). Eligibility: \- Individuals at least 18 years of age who have been diagnosed with metastatic melanoma that has not responded to previous IL-2 treatment. Design:
• Participants will be screened with a physical examination and medical history, tumor imaging studies, and heart and lung function tests.
• Prior to treatment, participants will have an intravenous catheter inserted into the chest to administer the study drugs.
• Participants will have leukapheresis to provide white blood cells for laboratory modification.
• Seven days before the start of the treatment, participants will be admitted to the hospital to have chemotherapy with cyclophosphamide and fludarabine. These drugs will suppress the immune system to improve the effects of the treatment.
• One to four days after the last dose of chemotherapy, participants will receive the modified cells. Participants in the group that will receive IL-2 will begin to receive the treatment 24 hours after the cell infusion, every day for 5 days. All participants will receive filgrastim injections to help the body produce more white blood cells.
• Participants will recover in the hospital for about 7 to 12 days after the cell infusion or the last dose of IL-2. Participants will continue to receive medications and provide blood and tumor samples for testing.
• Participants will have regular followup visits to assess the effects of the treatment.

Conditions

Metastatic Cutaneous Melanoma

Keywords

Skin Cancer; Malignancy; Immunotherapy; Melanoma Peptides; Melanoma; Metastatic Melanoma

Outcome Measures

Primary Outcomes (2)

• Clinical Response

  Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression disease (PD) is at least a 20 % increase in the sum of the LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.

  7 months

• Safety of Drosophila Generated PBL Administered in Combination With a Lymphodepleting Preparative Regimen and Supportive Systemic Aldesleukin

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

  7 months

Secondary Outcomes (1)

• Investigate Low-dose Systemic Aldesleukin to Cell Efficacy

  7 months

Study Arms (3)

Cohort 0

EXPERIMENTAL

Drosophila generated CTL + SQ IL-2 Drug: 1 fludarabine, cyclophosphamide, Drosophila-peptide pulsed Melanoma-reactive autologous CD8+ peripheral blood lymphocytes (PBL) (CTL-05), aldesleukin Fludarabine 25 mg/m\^2 x 5 days Cyclophosphamide 60 mg/kg intravenous (IV) x2 days, Up to 1x10e10 CTL-05 cells Aldesleukin 125,000 IU/kg/dose as a daily subcutaneous injection

Drug: fludarabine; Drug: cyclophosphamide; Drug: Drosophila-peptide pulsed Melanoma-reactive autologous CD8+ PBL; Drug: Aldesleukin

Cohort 1

EXPERIMENTAL

2 Experimental Lymphodepleting regimen +Cells+Low dose IL-2 Drug: 2 fludarabine, cyclophosphamide, Drosophila-peptide pulsed Melanoma-reactive autologous CD8+ peripheral blood lymphocytes (PBL), aldesleukin Fludarabine 25 mg/m\^2 x 5 days Cyclophosphamide 60 mg/kg intravenous (IV) x2 days, Up to 1x10e10 CTL-05 cells Aldesleukin 125,000 IU/kg/dose as a daily subcutaneous injection

Drug: fludarabine; Drug: cyclophosphamide; Drug: Drosophila-peptide pulsed Melanoma-reactive autologous CD8+ PBL; Drug: Aldesleukin

Cohort 2

EXPERIMENTAL

1 Experimental Lymphodepleting regimen +Cells Drug: 3 fludarabine, cyclophosphamide, Drosophila-peptide pulsed Melanoma-reactive autologous CD8+ peripheral blood lymphocytes (PBL) Fludarabine 25 mg/m\^2 x 5 days Cyclophosphamide 60 mg/kg intravenous (IV) x2 days, Up to 1x10e10 CTL-05 cells

Drug: fludarabine; Drug: cyclophosphamide; Drug: Drosophila-peptide pulsed Melanoma-reactive autologous CD8+ PBL; Drug: Aldesleukin

Interventions

fludarabine DRUG

Fludarabine 25 mg/m\^2 x 5 days

Also known as: Fludara

Cohort 0; Cohort 1; Cohort 2

cyclophosphamide DRUG

Cyclophosphamide 60 mg/kg intravenous (IV) x 2 days

Also known as: Cytoxan

Cohort 0; Cohort 1; Cohort 2

Drosophila-peptide pulsed Melanoma-reactive autologous CD8+ PBL DRUG

Up to 1x10e10 CTL-05 cells

Cohort 0; Cohort 1; Cohort 2

Aldesleukin DRUG

Aldesleukin 125,000 IU/kg/dose as a daily subcutaneous injection

Also known as: IL-2

Cohort 0; Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic cutaneous melanoma with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Previously received high dose-aldesleukin and have been either non-responders (progressive disease) or have recurred.
• Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.
• Greater than or equal to 18 years of age.
• Able to understand and sign the Informed Consent Document
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Life expectancy of greater than three months.
• Patients of both genders must be willing to practice a highly effective method of birth control during and for four months following treatment
• Patients must be HLA-A\*0201 positive
• Serology:
• 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 and hepatitis C antibody unless antigen negative.
• Hematology:
• Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim.
• White blood cell (WBC) (\> 3000/mm\^3).

You may not qualify if:

• Active systemic infections, coagulation disorders or other active major medical illnesses.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• Requirement for systemic steroid therapy
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• History of coronary revascularization or ischemic symptoms
• Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
• Documented LVEF of less than or equal to 45% tested in patients with:
• Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
• Age greater than or equal to 60 years old
• Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:
• A prolonged history of cigarette smoking (20 pk/yrs of smoking)
• Symptoms of respiratory dysfunction
• Pregnant or nursing women

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, Urist M, McMasters KM, Ross MI, Kirkwood JM, Atkins MB, Thompson JA, Coit DG, Byrd D, Desmond R, Zhang Y, Liu PY, Lyman GH, Morabito A. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001 Aug 15;19(16):3622-34. doi: 10.1200/JCO.2001.19.16.3622.

  PMID: 11504744 BACKGROUND

• Smith FO, Downey SG, Klapper JA, Yang JC, Sherry RM, Royal RE, Kammula US, Hughes MS, Restifo NP, Levy CL, White DE, Steinberg SM, Rosenberg SA. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res. 2008 Sep 1;14(17):5610-8. doi: 10.1158/1078-0432.CCR-08-0116.

  PMID: 18765555 BACKGROUND

• Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ, Jones SA, Mangiameli DP, Pelletier MM, Gea-Banacloche J, Robinson MR, Berman DM, Filie AC, Abati A, Rosenberg SA. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005 Apr 1;23(10):2346-57. doi: 10.1200/JCO.2005.00.240.

  PMID: 15800326 BACKGROUND

MeSH Terms

Conditions

Melanoma; Skin Neoplasms; Neoplasms

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; aldesleukin; Interleukin-2

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: James Yang, M.D.
• Organization: National Cancer Institute, National Institutes of Health

jamesyang@mail.nih.gov

301-496-1574

Study Officials

• James Yang, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 6, 2011
• First Posted: January 7, 2011
• Study Start: April 15, 2011
• Primary Completion: December 8, 2011
• Study Completion: December 8, 2011
• Last Updated: August 1, 2017
• Results First Posted: December 13, 2012

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)