Protocol Number: 00-C-0201

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

Number:

00-C-0201

Summary:

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.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility 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.

Special Instructions: Currently Not Provided

Keywords:

Immunoablative

Mobilization

Apheresis

Recruitment Keywords:

Multiple Myeloma

IgG Multiple Myeloma

IgA Multiple Myeloma

Conditions:

Multiple Myeloma

Investigational Drug(s):

Myeloma Immunoglobulin Idiotype Vaccine

GM-CSF

Investigational Device(s):

None

Contacts:

CSSC
Clinical Studies Support Center/NCI
164 Rollins Avenue
2nd FLoor
Rockville, MD 20852
Phone: (888) 624-1937
Fax: (301) 881-8239

Electronic Address: ncicssc@mail.nih.gov

Citations:

Antibody to a molecularly defined antigen confined to a tumor cell surface

Idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes: a therapeutic target

Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody

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