Study of MAGE-A3 and NY-ESO-1 Immunotherapy in Combo With DTPACE Chemo and Auto Transplantation in Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00090493
First received: August 26, 2004
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

The hope is that the peptide vaccines will stimulate the immune system to attack and kill the myeloma cells. The purpose is to generate anti-myeloma T-cells which will kill myeloma cells and nothing else.


Condition Intervention Phase
Multiple Myeloma
Biological: MAGE-A3
Biological: MAGE-A3 AND NY-ESO-1 IMMUNOTHERAPY
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: UARK 2003-26, A Pilot Study of MAGE-A3 and NY-ESO-1 Immunotherapy in Combination With DTPACE Chemotherapy and Autologous Transplantation in Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • The Number of Participants Experiencing a Response to the Peptide Vaccines. [ Time Frame: 2 week intervals ] [ Designated as safety issue: No ]
    The peptides are fragments from two proteins MAGE-A3 and NY-ESO-1. There will be a series of 12 peptide vaccinations given as a subcutaneous (beneath the skin) injection (vaccines) at 2 week intervals resulting in an immune response to myeloma. The tumor peptides used in the vaccines are unique to myeloma, and it is not expected that there will be an immune response to normal organs. Myeloma cells must express MAGE-A3 or NY-ESO-1, be severe enough to require chemotherapy and stem cell transplantation and have appropriate HLA tissue type.


Enrollment: 4
Study Start Date: June 2004
Study Completion Date: May 2012
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MAGE-A3 and NY-ESO-1 Immunotherapy
Treatment will consist of receiving peptide vaccinations as a shot just under the skin (subcutaneous). Peptides are small pieces of proteins. We have chosen to vaccinate with peptides derived from cancer proteins found in myeloma and other cancers. The purpose is to generate anti-myeloma T-cells which will kill myeloma cells and nothing else.
Biological: MAGE-A3
vaccinations at 2- week intervals (days 22,36,50) with the MAGE-A3 or NY-ESO-1 peptide and GM-CSF adjuvant. The peptides will be given s.c. in a dose of 300μg; GM-CSF (250μg) will be administered to promote attraction, maturation and longevity of DCs. #2 will be thawed and re-infused after transplant on day 81 and any anti-myeloma T-cells in this leukapheresis product will be boosted immediately by re-vaccinating the patient 3 times at 14 day intervals (vaccination #4-6: days 82, 96, and 110). Vaccines #4-6 will be identical to vaccines 1-3. Thereafter, 6 monthly vaccines will be given to further boost the anti-MM-T-cells.
Biological: MAGE-A3 AND NY-ESO-1 IMMUNOTHERAPY
Three injections with 300µg per injection (in 1.5mls) of peptide will be given subcutaneously together with the adjuvant GM-CSF at 500µg (same site in 0.5 mls) at two-week intervals

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • MM patients who have active, symptomatic myeloma, and meet the criteria below thus establishing the presence of high-risk myeloma
  • MM Salmon-Durie Stage: IA&B (with abnormal cytogenetics*), IIA, IIB, IIIA, and IIIB, and meet the criteria below thus establishing the presence of high-risk myeloma
  • MM must meet one of the following criteria: a) Patients who have MAGE-A3 positive MM and who have the tissue type HLA-A*0101, or -* B35, are allocated to receive the MAGE-A3168-176 peptide vaccine. b) Patients who have NY-ESO-1 positive MM and who have the tissue type HLA-A*0201 are allocated to the NY-ESO-1156-C165V peptide vaccine. c) Patients who have NY-ESO-1 positive and MAGE-A3 negative or positive MM and who have as tissue type HLA-A*0101, or -* B35 and HLA-A*0201, will receive vaccination with the NY-ESO-1156-C165V peptide vaccine. d) Patients who have NY-ESO-1 negative and MAGE-A3 positive MM and who have as tissue type HLA-A*0101, or -* B35 and HLA-A*0201, will receive vaccination with the MAGE-A3 peptide vaccine.
  • Karnofsky performance score ≥=70, unless bone pain caused by MM results in a Karnofsky score of > or =50.
  • Age 18-70 years old
  • Hb > or =8.0gm/dl, ANC > or =1,000/microliters, platelet count > or = 100,000/microliters.
  • Patients must have signed an IRB-approved consent form and been informed about the investigational nature of the study
  • Negative serology for HIV, Hepatitis C and negative for Hepatitis B surface antigen.
  • CD4+ count >400/microliters
  • Life expectancy > 6 months
  • Negative pregnancy test and females agree to two forms of contraception or abstinence.
  • Provisional insurance approval for single or double auto-transplant(s)

Exclusion Criteria:

  • MGUS, indolent and smoldering myeloma
  • Chemotherapy or other immunosuppressive treatment e.g. gluco-corticosteroids, cyclophosphamide, methotrexate within the 4 weeks prior to enrollment
  • Patients who have malignancies other than carcinoma-in-situ of the cervix or non-melanomatous skin cancer
  • Fever or active infection
  • Liver function: total bilirubin > 2.5xULN or AST/ALT >2.5xULN
  • Renal function: patients on dialysis, or serum creatinine >2.0mg/dl
  • Simultaneous treatment with a second investigational drug or biologic agent for MM
  • Other intercurrent serious illness, e.g. cardiac, pulmonary, hepatic disease, uncontrolled diabetes, etc
  • Cardiac: Patients with recent (< or =6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrythmias are ineligible. Ejection fraction by ECHO or must be > or = 50% and must be performed within 60 days prior to registration, unless the patient has received chemotherapy within that period of time (dexamethasone and thalidomide excluded), in which case the LVEF must be repeated
  • Pulmonary: Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease resulting in unacceptable lung function: patients must have adequate pulmonary function studies > or = 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > or = 50% of predicted. Patients unable to complete pulmonary function tests due to myeloma related pain or fracture must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70
  • Patients must be able to receive full doses of DT PACE, in the opinion of the treating investigator, with the exception of: A) Patients that have received prior adriamycin > 450 mg/m2 and LVEF < 55%. Adriamycin will be omitted in these patients. B) Patients with a creatinine clearance 30 - 50 ml/minute, who will receive 50% of the cisplatin dose
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00090493

Locations
United States, Arkansas
University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Frits van Rhee, M.D., Ph.D. Myeloma Institute for Research & Therapy
  More Information

Additional Information:
No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT00090493     History of Changes
Other Study ID Numbers: UARK 2003-26
Study First Received: August 26, 2004
Results First Received: January 25, 2013
Last Updated: May 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arkansas:
Myeloma
Mage-A3
Transplant
Peptide
DTPACE
vaccines
Immunotherapy
NY-ESO-1

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014