Vaccine Therapy Following Therapeutic Autologous Lymphocytes and Cyclophosphamide in Treating Patients With Metastatic Melanoma

NCT01339663 | Completed Phase 1 DMC

• 3 other identifiers: 2481.00NCI-2011-00383K12CA076930
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of autologous T-antigen-presenting cells (T-APC) vaccine following therapeutic autologous lymphocytes (CTL) and cyclophosphamide in treating patients with metastatic melanoma. Aldesleukin may stimulate lymphocytes, such as CTL, to kill melanoma cells. Treating lymphocytes with aldesleukin in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Vaccines made from melanoma antigen may help the body build an effective immune response to kill tumor cells and may boost the effect of the CTL. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving T-APC vaccine after CTL and cyclophosphamide may be an effective treatment for melanoma

Conditions

Recurrent Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (2)

• Treatment-related dose limiting toxicity (DLT) as defined by Grade 3 or greater unexpected toxicity by the NCI Common Toxicity Criteria (CTC) v4.0

  Assessed at the maximum tolerated dose (MTD) or dose level immediately below the dose level for which the incidence of DLT was less than 35%.

  Up to 8 weeks after the T cell infusion

• In vivo persistence of adoptively transferred T cells

  Assessed by intrapatient comparison between the first (without T-APC) and second (with T-APC) CTL infusion. Descriptive statistics will be applied and t-tests of intrapatient in vivo T cell persistence between the two Infusions will be determined.

  At 4 weeks

Secondary Outcomes (1)

• Clinical response

  Up to 8 weeks after second dose

Study Arms (1)

Treatment (dose-escalation, T-APC boost, CTL)

EXPERIMENTAL

INFUSION I: Patients receive high-dose cyclophosphamide IV on day days -4 and -3 and low-dose IL-2 SC BID on days 0-14. Patients also receive CTL IV on day 0. INFUSION II: Beginning 6-48 hours later, patients receive high-dose cyclophosphamide, low-dose IL-2, and CTL as in Infusion I. Patients also receive T-APC vaccine IV within 18-36 hours following CTL infusion and in week 4, and IL-2 SC BID on days 0-14 following second T-APC vaccination.

Drug: cyclophosphamide; Biological: aldesleukin; Biological: autologous tumor cell vaccine; Other: laboratory biomarker analysis; Other: immunologic technique; Other: immunohistochemistry staining method; Genetic: polymerase chain reaction; Biological: therapeutic autologous lymphocytes

Interventions

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (dose-escalation, T-APC boost, CTL)

aldesleukin BIOLOGICAL

Given SC

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Treatment (dose-escalation, T-APC boost, CTL)

autologous tumor cell vaccine BIOLOGICAL

Receive T-APC via IV

Also known as: AC vaccine, ATCV, Autologous Cell Vaccine

Treatment (dose-escalation, T-APC boost, CTL)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (dose-escalation, T-APC boost, CTL)

immunologic technique OTHER

Correlative studies

Also known as: immunological laboratory methods, laboratory methods, immunological

Treatment (dose-escalation, T-APC boost, CTL)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment (dose-escalation, T-APC boost, CTL)

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Treatment (dose-escalation, T-APC boost, CTL)

therapeutic autologous lymphocytes BIOLOGICAL

Receive adoptively transferred CD8+ antigen-specific T cell clones via IV

Also known as: AL, Autologous Lymphocytes, autologous T cells

Treatment (dose-escalation, T-APC boost, CTL)

Eligibility Criteria

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

You may qualify if:

• Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease
• Tumor expression of melanocyte differentiation antigen (MDA: MART-1 = 2+ staining or \> 25%) by immunohistochemistry (IHC)
• Expression of human leukocyte antigen (HLA)-A201
• Zubrod performance status of '0-1' at the time of treatment
• Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography \[CT\] scan)
• Normal cardiac stress test will be required for all patients with any history of cardiac disease

You may not qualify if:

• Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry
• Serum creatinine \> 1.6 mg/dL or Creatinine clearance \< 75 ml/min
• Serum glutamic oxaloacetic transaminase (SGOT) \> 150 IU or \> 3x upper limit of normal
• Bilirubin \> 1.6 mg/dL
• Prothrombin time \> 1.5 x control
• Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) \< 2.0 L or carbon monoxide diffusing capacity (DLco) (corr for hemoglobin \[Hgb\]) \< 75% will be excluded
• Congestive heart failure
• Clinically significant hypotension
• Symptoms of coronary artery disease
• Presence of cardiac arrhythmias on electrocardiograph (EKG) requiring drug therapy
• Ejection fraction \< 50 % (echocardiogram or multi gated acquisition scan \[MUGA\])
• Symptomatic central nervous system metastases greater than 1 cm at time of therapy; patients with 1-2 asymptomatic, less than 1 cm brain/central nervous system (CNS) metastases without significant edema may be considered for treatment
• Patients with active infections or oral temperature \> 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy
• Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell therapy)
• Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be recently polymerase chain reaction (PCR)+ for hepatitis are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed immune system found in these infected patients and the possibility of premature death would compromise study objectives

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; aldesleukin; Interleukin-2; FANG vaccine; Immunologic Techniques; Immunohistochemistry; Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; 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; Investigative Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Nucleic Acid Amplification Techniques; Genetic Techniques

Study Officials

• Sylvia Lee

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: April 21, 2011
• Study Start: March 1, 2012
• Primary Completion: December 1, 2012
• Last Updated: April 21, 2014

Record last verified: 2014-04

Locations

US (1)