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90 Y-BC8-DOTA Monoclonal Antibody, Fludarabine Phosphate, and Total-Body Irradiation Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma

Complete title: A Phase I Study of 90Y-BC8-DOTA monoclonal antibody, Fludarabine and TBI Followed by HLA-Matched, Allogeneic Peripheral Blood Stem Cell Transplant for the Treatment of Multiple Myeloma

Research Study Number       2450.00
Principal Investigator       Damian Green, MD
Phase       I

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Research Study Description

This phase I trial studies the side effects and best dose of yttrium Y 90 anti-CD45 monoclonal antibody BC8 when given together with fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant in treating patients with multiple myeloma. Radiolabeled monoclonal antibodies, such as yttrium Y 90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving yttrium Y 90 anti-CD45 monoclonal antibody BC8, fludarabine phosphate, and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening and may be an effective treatment for multiple myeloma.

Eligibility Criteria (must meet the following to participate in this study)

Ages Eligible for Study: 18 Years to 65 Years (Adult)

Genders Eligible for Study: Both

- Patients must have history of symptomatic myeloma requiring treatment and meet one of the following requirements:

-- * Have at least 1 high risk feature at diagnosis (including deletion 13 or hypodiploidy by conventional cytogenetics, t(4;14), t(14;16) or deletion 17 by fluorescence in situ hybridization [FISH], beta 2 microglobulin > 3.5, lactate dehydrogenase [LDH] greater than 1.5 x upper limit of normal [ULN], history of plasma cell leukemia) (prior to chemotherapy); OR

-- * Have progressive disease on primary therapy with or without prior autologous stem cell transplant; OR

-- * Have persistent or progressive disease following autologous transplant; it is acceptable for these patients to have a second transplant for disease reduction

- Bone marrow cellularity of >= 50% of age defined normal values by core biopsy; cellularity must be evaluated within 90 days of the dosimetry infusion and at least 21 days after receiving any cytoreductive/myelosuppressive chemotherapy

- Eastern Cooperative Oncology Group (ECOG) =< 2

- Measured creatinine clearance > 50 ml/min or estimated creatinine clearance > 50 ml/min

- For females of childbearing potential, must have a negative pregnancy test

- Patients must have a human leukocyte antigen (HLA)-matched related donor or an unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) donation, or bone marrow donation as follows:

-- * Related donor related to the patient and genotypically or phenotypically identical for HLA-A, B, C, DRB1 and DQB1; phenotypic identity must be confirmed by high-resolution typing

-- * Unrelated donor:

--- ** Matched for HLA-A, B, C, DRB1 DQB1 by high resolution typing; OR

--- ** Mismatched for a single allele without antigen mismatching at HLA-A, B, or C as defined by high resolution typing but otherwise matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing

--- ** Patient and donor pairs homozygous at a mismatched allele, in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed

-- * Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion

- Ability to provide informed consent

- DONOR: Patients must have an HLA matched donor as well as standard Seattle Cancer Care Alliance (SCCA) and or National Marrow Donor Program (NMDP)/other donor center criteria for PBSC donation

- DONOR: Donors must consent and be eligible to undergo granulocyte colony-stimulating factor (GCSF) mobilization and PBSC harvest; marrow is not allowed as a source of stem cells on this study

Other eligibility criteria may apply.

Exclusions (conditions that would prevent participation in this study)

- Patients with the following organ dysfunction:

-- * Left ventricular ejection fraction < 35%

-- * Corrected diffusion capacity of carbon monoxide (DLCO) < 35% or receiving supplemental continuous oxygen

-- * Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidences by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease

- Pregnant or breast-feeding females

- Circulating antibody against mouse immunoglobulin (HAMA)

- Prior allogeneic transplant

- Plasmacytomas > 1 cm in marrow areas measured by magnetic resonance imaging (MRI) or extramedullary plasmacytomas (radiated lesions are exempt from this criteria); patients may receive cytoreductive therapy, including allogeneic stem cell transplant (ASCT) (if high risk) or second ASCT (if failed a prior ASCT) to achieve disease control, but may not receive any cytoreductive therapy within 30 days of the dosimetry infusion and must have bone marrow cellularity meeting inclusion criteria obtained at least 21 days after any cytoreductive/myelosuppressive chemotherapy was last administered

- Prior radiation to maximally tolerated levels to any critical normal organ, or > 20 Gy prior radiation to large areas of the bone marrow (e.g., external radiation therapy to whole pelvis)

- Patients who are known to be seropositive for human immunodeficiency virus (HIV)

- Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant

- Active central nervous system (CNS) disease at the time of treatment

Other exclusion criteria may apply.

Research Study Number       2450.00
Contact       Seattle Cancer Care Alliance Intake Office
Telephone       800-804-8824 / 206-288-1024

Hematologic Malignancies; Lymphoproliferative Disorders; Multiple Myeloma (MM); Neoplasms; Immunoproliferative Disorders; Cardiovascular Diseases; Neoplasms, Plasma Cell; Paraproteinemias; Immune System Diseases; Plasma Cell Myeloma

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Please remember:

  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.

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