Clinical Trial: Evaluation of Cellular and Humoral Immunity Against the Idiotype in Multiple Myeloma Patients Undergoing Autologous Transplantation After Idiotype Vaccination in an Attempt to Decrease the Risk of Relapse

This study is no longer recruiting patients.

Sponsored by: National Cancer Institute (NCI)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

Although high-dose chemoradio therapy with autologous stem cell transplantation has shown some promise in the management of patients with multiple myeloma, relapse of the underlying disease remains the primary cause of treatment failure. This pilot study to explore the possibility that active-specific immunotherapy may be effective in eliminating minimal residual disease remaining after high dose therapy. Experimental studies in patients with lymphoma, as well as a single patient with myeloma have demonstrated the feasibility of immunoglobulin idiotype s a tumor specific antigen for development of therapeutic vaccines against B-cell malignancies. Patients will be immunized with myeloma idiotype protein, made immunogenic by conjugation to a carrier (KLH) and administration with GM-CSF as an immunological adjuvant, at several time points before and after high-dose therapy. The objective of this study is to test whether cellular and humoral immunity can be induced against the unique idiotype expressed on the patient's myeloma pre- and post-transplantation. Patients will receive a series of 3 vaccinations with myeloma Id-KLH (0.5mg) administered s.c. together with GM-CSF (250 ug/m2) for 4 consecutive days 2, 3, and 6 months after high dose therapy with either melphalan/TBI or melphalan/cytoxan followed by autologous peripheral mononuclear stem cell transplantation.

Condition Treatment or Intervention Phase
Multiple Myeloma
 Drug: Myeloma Immunoglobulin Idiotype Vaccine
 Drug: GM-CSF
Phase II

MedlinePlus related topics:  Multiple Myeloma

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Further Study Details: 

Expected Total Enrollment:  60

Study start: November 21, 1996

Although high-dose chemoradiotherapy with autologous stem cell transplantation has shown some promise in the management of patients with multiple myeloma, relapse of the underlying disease remains the primary cause of treatment failure. This pilot study to explore the possibility that active-specific immunotherapy may be effective in eliminating minimal residual disease remaining after high dose therapy. Experimental studies in patients with lymphoma, as well as a single patient with myeloma have demonstrated the feasibility of immunoglobulin idiotype s a tumor specific antigen for development of therapeutic vaccines against B-cell malignancies. Patients will be immunized with myeloma idiotype protein, made immunogenic by conjugation to a carrier (KLH) and administration with GM-CSF as an immunological adjuvant, at several timepoints before and after high-dose therapy. The objective of this study is to test whether cellular and humoral immunity can be induced against the unique idiotype expressed on the patient's myeloma pre- and post-transplantation. Patients will receive a series of 3 vaccinations with myeloma Id-KLH (0.5mg) administered s.c. together with GM-CSF (250 micrograms/m2) for 4 consecutive days 2, 3, and 6 months after high dose therapy with either melphalan/TBI or melphalan/cytoxan followed by autologous peripheral mononuclear stem cell transplantation.

Eligibility

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Patients with IgG or IgA multiple myeloma who are classified as low-or-intermediate-risk on the basis of the following University of Arkansas algorithm are eligible:
a) cytogenetics: no translocations, no 11q, no-13/13q-
and
b) beta-2 microglobulin less than 2.5 mg/L pre-AT#1.
Patients who attain at least a PR prior to second transplantation are eligible.
All previous therapy must be completed at least eight weeks prior to scheduled second transplantation.
Patients should have recovered from all hematologic and non-hematologic toxicity of previous therapy.
Steroids must be discontinued at least four weeks prior to vaccination.
Patients must meet the following criteria:
Karnofsky performance status greater than or equal to 70%.
Life expectancy greater than 8 weeks, and absence of co-existing medical problems which would significantly increase the risk of the transplant procedure in the judgment of the bone marrow transplant attending physicians.
Creatinine less than 2.0 normal and not rising, for at least 2-4 weeks before transplantation. If creatinine is elevated, then creatinine clearance must be greater than 40 ml/min.
Direct bilirubin less than 2 mg/dl, SGOT less than or equal to 4 times top normal, and none of these parameters increasing, for at least 2-4 weeks before transplantation.
Patients must be HIV-negative.
M-protein concentration in the harvested plasma must be greater than 50% of the total Ig of the corresponding isotype. M-protein must be able to be purified by either protein A- or anti-IgA-sepharose.
Age greater than or equal to 18 years.
Patients must not be pregnant or lactating. Patients of childbearing potential must use an effective method of contraception.
Patients must not have received an autotransplant with CD34 selected stem cells.

Location Information


Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States

More Information

Detailed Web Page

Publications

Barlogie B, Epstein J, Selvanayagam P, Alexanian R. Plasma cell myeloma--new biological insights and advances in therapy. Blood. 1989 Mar;73(4):865-79. Review.

Barlogie B, Alexanian R, Jagannath S. Plasma cell dyscrasias. JAMA. 1992 Nov 25;268(20):2946-51. Review. No abstract available.

Gregory WM, Richards MA, Malpas JS. Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol. 1992 Feb;10(2):334-42.

Study ID Numbers:  970033; 97-C-0033
Record last reviewed:  October 1, 2004
Last Updated:  November 23, 2004
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001562
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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