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

NCT00090493 | Completed Phase 2 Results

• 1 other identifier: UARK 2003-26
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Myeloma; Mage-A3; Transplant; Peptide; DTPACE; vaccines; Immunotherapy; NY-ESO-1

Outcome Measures

Primary Outcomes (1)

• The Number of Participants Experiencing a Response to the Peptide Vaccines.

  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.

  2 week intervals

Study Arms (1)

MAGE-A3 and NY-ESO-1 Immunotherapy

EXPERIMENTAL

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; Biological: MAGE-A3 AND NY-ESO-1 IMMUNOTHERAPY

Interventions

MAGE-A3 BIOLOGICAL

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.

MAGE-A3 and NY-ESO-1 Immunotherapy

MAGE-A3 AND NY-ESO-1 IMMUNOTHERAPY BIOLOGICAL

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

MAGE-A3 and NY-ESO-1 Immunotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (1)

University of Arkansas for Medical Sciences/MIRT

Little Rock, Arkansas, 72205, United States

Location

Related Links

• Myeloma Institute for Research \& Therapy website

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

MAGEA3 protein, human

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Frits van Rhee, MD, PhD
• Organization: University of Arkansas for Medical Sciences - MIRT

vanrheefrits@uams.edu

(501) 686-8230

Study Officials

• Frits van Rhee, M.D., Ph.D.

  Myeloma Institute for Research & Therapy

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2004
• First Posted: August 31, 2004
• Study Start: June 1, 2004
• Primary Completion: July 1, 2007
• Study Completion: May 1, 2012
• Last Updated: June 24, 2013
• Results First Posted: June 24, 2013

Record last verified: 2013-05

Locations

US (1)