Melanoma Treatment With White Blood Cells That Destroy MART Expressing Tumor Cells

NCT01495572 | Terminated Phase 2 Results DMC

• 2 other identifiers: 12004512-C-0045
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Some cancer treatments collect a patient s own blood cells to use as specialized cancer-fighting cells. Collected white blood cells known as PBL (peripheral blood lymphocytes) can use to isolate special cells that can fight tumors. Before treatment with PBL, chemotherapy is given to destroy existing white blood cells so that the new cells can survive and attack the tumors. After PBL treatment, aldesleukin is given to help the new cells grow. Researchers want to see if special white blood cells that recognize a specific protein that is present in melanoma cells (melanoma antigen recognized by T cells (MART)) can cause tumors to shrink. These white blood cells will be tested with and without aldesleukin. Objectives:

• To test the safety and effectiveness of white blood cells that target MART in the treatment of melanoma.
• To test white blood cells that target MART with and without aldesleukin. Eligibility: \- Individuals at least 18 years of age who have melanoma that has not responded to standard treatments. Design:
• Participants will be screened with a medical history and physical exam. Blood and urine samples will be taken. Imaging studies such as x-rays or magnetic resonance imaging scans will be performed.
• Participants will provide white blood cells through leukapheresis. Researchers will attempt to isolate white blood cells that recognize MART
• Seven days before the start of treatment, participants will have chemotherapy.
• After the last dose of chemotherapy, participants will receive the MART reactive PBL cells. Filgrastim doses will also be given to help white blood cell counts return to normal. Participants will have frequent blood tests.
• Participants who are able to have aldesleukin treatment will start within 24 hours after receiving the MART reactive PBL cells. Treatment will continue for up to 5 days.
• Participants may have an optional tumor or lymph node biopsy to study the effects of treatment.
• If the tumor continues to grow after MART PBL treatment, participants may have one more round of cell collection and treatment.
• Participants will have followup visits for up to 6 months after receiving the MART reactive PBL treatment.

Conditions

Metastatic Melanoma; Skin Cancer

Keywords

Malignant Melanoma; Immunotherapy; Cell Therapy; HLA-A2 Positive; Skin Cancer

Outcome Measures

Primary Outcomes (2)

• Clinical Tumor Response

  Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial response (PR) is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new 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 diameters while on study.

  One year

• Number of Participants With Adverse Events

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

  10 months

Study Arms (2)

High Dose (HD) Aldesleukin

EXPERIMENTAL

Pts receiving high dose aldesleukin: Cyclophosphamide 60 mg/kg intravenous (IV) for days -7 and -6, Fludarabine 25 mg/m\^2 IV for days -5 to -1, plus melanoma antigen recognized by T cells (MART)-127-35 reactive CD8+ peripheral blood lymphocytes (PBL) up to 3x10\^11 IV over 20-30 minutes on day 0, plus aldesleukin 720,000 IU/kg IV over 15 minutes, every 8 hrs for up to 5 days.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Aldesleukin; Drug: MART-1 Reactive CD8+ PBL

Peripheral Blood Lymphocytes (PBL)

EXPERIMENTAL

Cyclophosphamide 60 mg/kg intravenous (IV ) for days -7 and -6, Fludarabine 25 mg/m\^2 IV for days -5 to -1, plus MART-127-35 reactive CD8+ PBL up to 3x10\^11 IV over 20-30 minutes on day 0

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MART-1 Reactive CD8+ PBL

Interventions

Fludarabine DRUG

25 mg/m\^2 IV (in the vein) for 5 days (day -5 to -1)

High Dose (HD) Aldesleukin; Peripheral Blood Lymphocytes (PBL)

Cyclophosphamide DRUG

60 mg/kg IV (in the vein) for days -7 and -6

High Dose (HD) Aldesleukin; Peripheral Blood Lymphocytes (PBL)

Aldesleukin DRUG

Only given to patients assigned to high dose (HD) Arm - 720,000 IU/kg intravenous (IV) over 15 minutes, every 8 hrs (+/- 1 hr) for up to 5 days (max 15 doses).-6

High Dose (HD) Aldesleukin

MART-1 Reactive CD8+ PBL DRUG

Intravenous (IV) over 30 minutes on day 0

High Dose (HD) Aldesleukin; Peripheral Blood Lymphocytes (PBL)

Eligibility Criteria

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

You may qualify if:

• Measurable metastatic melanoma.
• Confirmation of diagnosis of metastatic melanoma and positivity for melanoma antigens recognized by T cells (MART) confirmed by the Laboratory of Pathology of the National Cancer Institute (NCI).
• 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.
• Patients must be refractory to high dose aldesleukin treatment.
• NOTE: This is not required for patients with non-cutaneous melanoma, patients for whom high dose aldesleukin is medically contraindicated or for patients who are unwilling to receive high dose aldesleukin.
• MART-1:27-35 reactive peripheral blood lymphocytes derived from a leukapheresis.
• Human leukocyte antigens (HLA-A) 0201 positive.
• Greater than or equal to 18 years of age and less than or equal to age 70.
• Both genders must be willing to practice birth control during treatment and for four months after receiving the preparative regimen.
• Life expectancy of greater than three months.
• Willing to sign a durable power of attorney.
• Able to understand and sign the Informed Consent Document.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1 for the high-dose aldesleukin cohort or ECOG 0, 1 or 2 for no aldesleukin cohort.
• Hematology:
• Absolute neutrophil count greater than 1000/mm\^3 without support of filgrastim

You may not qualify if:

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• Systemic steroid therapy required.
• Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• 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.)
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• The following patients will be excluded from the high-dose aldesleukin arm (but may be eligible for cells alone arm):
• History of coronary revascularization or ischemic symptoms
• Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45 percent.
• Documented LVEF of less than or equal to 45 percent 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 in 1 second (FEV1) less than or equal to 60 percent predicted tested in patients with:
• A prolonged history of cigarette smoking (20 pk/yrs of smoking within the past 2 years)
• Symptoms of respiratory dysfunction

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)

• Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

  PMID: 17237035 BACKGROUND

• Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb 1;109(3):455-64. doi: 10.1002/cncr.22427.

  PMID: 17200963 BACKGROUND

• Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008 Apr;8(4):299-308. doi: 10.1038/nrc2355.

  PMID: 18354418 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

fludarabine; Cyclophosphamide; aldesleukin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; 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

Limitations and Caveats

Due to slow accrual, the investigator decided to close the study.

Results Point of Contact

• Title: Udai Kammula M.D.
• Organization: National Cancer Institute

kammulau@mail.nih.gov

301-435-8606

Study Officials

• Udai S Kammula, 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 16, 2011
• First Posted: December 20, 2011
• Study Start: December 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: October 15, 2015
• Results First Posted: June 10, 2014

Record last verified: 2015-10

Locations

US (1)