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
Summary
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-DOTATissue localization of 111In-BC8-DOTA Ab
Secondary outcome: Disease responseDisease-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.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
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
ml/min
- 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
post-transplant
- 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
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