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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


Phase 1
18 Years
65 Years
Open (Enrolling)
Both
Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

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Trial Information

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


PRIMARY OBJECTIVES:

I. To assess the tissue localization of 111In-BC8-DOTA antibody therapy (Ab) and establish
reproducibly favorable biodistributions.

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.


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 greater than 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 greater than
3.5, lactate dehydrogenase [LDH] greater than 1.5 x upper limit of normal [ULN])
(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 percent of normal by core biopsy (25%
cellularity = 50% of normal)

- Eastern Cooperative Oncology Group (ECOG) less than or equal to 2

- Measured creatinine clearance greater than 50 ml/min or estimated creatinine
clearance greater than 50 ml/min

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

- Patients must have an human leukocyte antigen (HLA)-identical 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

- 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 SCCA and or
NMDP/other donor center criteria for PBSC donation; donors must consent and be
eligible to undergo 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 less than 35 percent

- Corrected diffusion capacity of carbon monoxide (DLCO) less than 35 percent 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 greater than 1cm 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
greater than 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Assessment of the tissue localization of 111In-BC8-DOTA Ab to establish reproducibly favorable biodistributions

Outcome Time Frame:

Up to 72 hours post infusion

Safety Issue:

No

Principal Investigator

William Bensinger

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2450.00

NCT ID:

NCT01503242

Start Date:

January 2012

Completion Date:

Related Keywords:

  • Refractory Multiple Myeloma
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109