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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

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Intervention: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure); Cyclosporine (Drug); Fludarabine Phosphate (Drug); Mycophenolate Mofetil (Drug); Peripheral Blood Stem Cell Transplantation (Procedure); Total-Body Irradiation (Radiation); Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 (Radiation)

Phase: Phase 1

Status: Recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Damian Green, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


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.

Clinical Details

Official 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

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

MTD of radiation delivered via 90 Y-BC8-DOTA

Tissue localization of 111In-BC8-DOTA Ab

Secondary outcome:

Disease response

Disease-free survival

Duration of remission

Overall survival

Detailed description: PRIMARY OBJECTIVES: I. To assess the tissue localization of 111In-BC8-DOTA antibody therapy (Ab) and establish reproducibly favorable biodistribution. II. To estimate the maximum tolerated dose (MTD) of radiation delivered via 90Y-BC8-DOTA Ab when combined with fludarabine phosphate (FLU) and 2 Gy total-body irradiation (TBI) as a preparative regimen followed by human leukocyte antigen (HLA)-matched, related or unrelated hematopoietic cell transplant (HCT) for patients with multiple myeloma. SECONDARY OBJECTIVES: I. To assess the potential efficacy of this approach, within the limits of a phase I study, by examining disease response, duration of remission, disease free survival (DFS), and overall survival (OS). OUTLINE: This is a dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody BC8 (90Y-BC8 Ab).

Patients receive 90Y-BC8 Ab intravenously (IV) on day - 12 and fludarabine phosphate IV on

days - 4 to -2. Patients undergo TBI and allogeneic peripheral blood stem cell transplant on

day 0. Patients also receive graft-vs-host disease prophylaxis comprising cyclosporine

orally (PO) twice daily (BID) on days - 3 to 56 with taper to day 180 or on days -3 to 100

with taper to 180; and mycophenolate mofetil IV or PO BID on days 0-27, or 0-40 with taper to 96. After completion of study treatment, patients are followed up every 6 months for 2 years, and then annually thereafter.


Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.


Inclusion Criteria:

- Patients must have history of symptomatic myeloma requiring treatment (defined as

significant anemia [hemoglobin (HgB) less than 10 gm/dl], renal dysfunction [creatinine > 2. 0] not attributable to other causes, lytic bone disease on imaging, or hypercalcemia) 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 at least 50% of normal by core biopsy (25% cellularity =

50% of normal)

- Eastern Cooperative Oncology Group (ECOG) =< 2

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


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

- Patients must have a human leukocyte antigen (HLA)-identical or 1 antigen mismatched

sibling donor or an HLA-matched 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, as follows:

- Sibling donor: A patient and sibling donor should be matched for HLA-A, B, C,

DRB1 and DQB1 by an intermediate resolution deoxyribonucleic acid (DNA)-based method; a 1-antigen mismatch, either bidirectional or unidirectional is acceptable

- Unrelated donor: An unrelated donor and recipient should be typed by a high

resolution DNA-based method, and ideally matched for HLA-A, B, C, DRB1 and DQB1 alleles, or if there is only a single locus disparity mismatched for an HLA-DQB1 antigen or allele; an unrelated donor may also be mismatched for any single 1) one HLA-A, B or C antigen or allele, or 2) HLA-DRB1 allele (with or without matching for HLA-DQB1)

- 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 Exclusion Criteria:

- 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

- 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


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

Locations and Contacts

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States; Recruiting
Damian J. Green, Phone: 206-667-5398, Email: dgreen@fhcrc.org
Damian J. Green, Principal Investigator
Additional Information

Starting date: January 2012
Last updated: July 31, 2015

Page last updated: August 20, 2015

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