Clinical Trial: Chemotherapy, Stem Cell Transplantation and Donor and Patient Vaccination for Treatment of Multiple Myeloma

This study is currently recruiting patients.

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

Purpose

This study will investigate the safety and effectiveness of a new treatment strategy for multiple myeloma using chemotherapy, stem cell transplantation and an anti-tumor vaccine. (Stem cells are "seed" cells produced by the bone marrow that develop into white and red blood cells and platelets.) Both the stem cell donor and the patient are immunized with a vaccine made from purified protein from the patient's tumor (myeloma). This vaccine cannot cause myeloma; it is intended to optimize the patient's chances of mounting an immune response against the tumor by boosting his or her own immune system and by transferring the donor's activated immunity through the donated cells. The vaccine also contains GM-CSF, a substance that boosts the immune system. Patients with myeloma and matched donors between the ages of 18 and 75 may be eligible for this study.

Patients will have a medical history, physical examination, blood tests (including testing for adequacy of the genetic match). A bone marrow aspiration and biopsy will also be done to evaluate disease status. These tests, done under a local anesthetic, use a special needle to draw out bone marrow from the hipbones. A central venous catheter (flexible plastic tube placed in a vein) will be put in place before treatment begins. It will be used to draw and transfuse blood, give anti-cancer drugs and other medications and collect plasma needed to make the vaccine. While the vaccine is being prepared, patients will receive chemotherapy to kill as many tumor cells as possible before the stem cells are transplanted. Fludarabine, etoposide, prednisone, vincristine, cyclophosphamide, and adriamycin will be given in 21-day treatment cycles consisting of 4 days of drugs followed by a 17-day rest period. The total number of cycles will depend on the individual patient's immune and disease status. After the vaccine has been produced, the donor has been vaccinated and donated the cells, and chemotherapy is completed-a process that may take up to 6 months-patients will be admitted to the hospital for the stem cell transplant. They will receive "transplant chemotherapy," consisting of the drugs cyclophosphamide and fludarabine for 4 days before the procedure. The donor's stem cells will then be infused through the central line. The drug cyclosporine will be given to prevent graft-versus-host disease, a potentially fatal condition in which the donated cells attack the patient's tissues. Patients will be monitored closely and discharged from the hospital when the cells have engrafted and the patient is strong enough to go home. They will receive vaccinations 3, 4 and 6 months after transplantation, along with GM-CSF injections under the skin on the day of the vaccination and for 3 consecutive days after the vaccination. At the time of the first vaccination, patients will undergo apheresis to collect white blood cells. Blood samples will be drawn at the time of each vaccination. Patients will be followed closely for the first 6 months after the transplant and then less frequently for at least 5 years. Follow-up visits may include bone marrow aspirates and biopsies, blood draws and other tests to monitor disease status and immune response to the vaccinations.

Stem cell donors will undergo a medical history, physical examination, and various blood tests (including testing for adequacy of the genetic match). Within 10 weeks of donating they will receive three vaccine injections under the skin, along with daily injections under the skin of GM-CSF. Injections of G-CSF-a substance causes stem cells to be released from the bone marrow-will also be given for 5 to 7 days before donating to maximize the number of cells that can be collected for transplantation. Stem cells will then be collected by leukapheresis, a procedure in which blood is withdrawn through a vein and circulated through a cell separator machine for collection and removal of the white cells, and the red cells and platelets are returned to the body.

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

Official Title: Active Immunization of Sibling Stem Cell Transplant Donors Against Purified Myeloma Protein of the Stem Cell Recipient with Multiple Myeloma in the Setting of Non-Myeloablative, HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation

Further Study Details: 

Expected Total Enrollment:  69

Study start: August 19, 2000

The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months. Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens. Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. Even with a reduction in treatment-related mortality, success with allogeneic SCT is limited by a significant risk of relapse. The goal of this protocol is to transfer tumor antigen-specific immunity induced in the stem cell donor to the allogeneic SCT recipient to reduce relapse. This would be performed using a non-myeloablative conditioning regimen to reduce treatment-related toxicity. Donors would be immunized with an Id vaccine prepared from the patient. Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim, which could potentially enhance the transfer tumor antigen specificity with the larger number of T cells in the allograft as compared to bone marrow. Donor immunization with myeloma Id in the setting of a non-myeloablative may represent a novel strategy for the treatment of multiple myeloma.

Eligibility

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA: Collection of plasma in recipient:
Patients with IgG or IgA multiple myeloma.
Patients have siblings.
HLA typing of recipient and donor(s) initiated.
Viral antibody screeing initiated.
INCLUSION CRITERIA:Recipient:
Patients with IgG or IgA multiple myeloma.
Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation. Patients who have undergone tandem autologous stem transplants are eligible if they meet all other eligibility criteria. Patients who have achieved at least a partial remission to initial (primary) conventional chemotherapy will be encouraged to proceed to autologous transplantation, but will also be eligible for this protocol.
Patients 18-75 years of age.
Karnofsky performance status greater than or equal to 80%.
Life expectancy greater than 6 months.
Left ventricular ejection fraction has to be greater than 50% by either MUGA or 2-D echo.
DLCO greater than 50% of the expected value when corrected for Hb.
Creatinine less than or equal to 1.5 mg/dl and a creatinine clearance greater than or equal to 50 ml/min.
Direct bilirubin less than or equal to 2.0 mg/dl SGOT less than 4x top normal.
M-protein: the concentration in the harvested plasma must be greater than 70% of the total Ig of the corresponding isotype.
Patients must be HIV-negative. Patients may be Hepatitis B core antigen positive, but surface antigen negative and without evidence of active infection. Patients must be Hepatitis C negative.
Not pregnant or lactating.
Patients of childbearing potential must use an effective method of contraception.
Consenting first degree relative matched at 6/6 or 5/6 HLA antigens, this may include a mismatch at the D locus.
Ability to give informed consent.
INCLUSION CRITERIA:Donor:
Age 18-75 years.
No physical contraindications to stem cell donation (i.e. severe atherosclerosis, auto-immune disease, cerebrovascular accident, active maliginancy.
Patients with severe atherosclerosis by history will receive a cardiology consult and be judged eligible on a case by case basis.
Donors must be HIV-negative, HBsAg-, and Hepatitis C antibody negative.
Not pregnant or lactating.
Donors of childbearing potential must use an effective method of contraception.
Normal CD4 and CD8 numbers as defined by Clinical Center standards.
Ability to give informed consent.

Location and Contact Information


Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Clinical Studies Support Center/NCI  1-888-624-1937    ncicssc@mail.nih.gov 

More Information

Detailed Web Page

Publications

Stevenson GT, Stevenson FK. Antibody to a molecularly-defined antigen confined to a tumour cell surface. Nature. 1975 Apr 24;254(5502):714-6. No abstract available.

Stevenson GT, Elliott EV, Stevenson FK. Idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes: a therapeutic target. Fed Proc. 1977 Aug;36(9):2268-71. No abstract available.

Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982 Mar 4;306(9):517-22. No abstract available.

Study ID Numbers:  000201; 00-C-0201
Record last reviewed:  December 1, 2004
Last Updated:  December 13, 2004
Record first received:  August 23, 2000
ClinicalTrials.gov Identifier:  NCT00006184
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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