OUTLINE: This is a dose-escalation study of 211At-OKT10-B10.
Patients receive 211At-OKT10-B10 intravenously (IV) continuously on days -7 to -4 and
melphalan via infusion on day -2. Patients then undergo peripheral blood stem cell (PBSC)
transplantation on day 0.
After completion of study treatment, patients are followed for 30 days, between 80 and 90
days, at 6, 9, 12, 18, and 24 months, and then annually thereafter.
Inclusion Criteria:
- Patients with a diagnosis of multiple myeloma
- Patients must have demonstrated at least a partial response (PR) according to the
International Myeloma Working Group (IMWG) criteria to at least one induction regimen
- Patients must have autologous hematopoietic stem cells collected with a minimum CD34+
stem cell yield of 8 x 10^6 CD34+ cells/kg of body weight (sufficient for two
autologous hematopoietic cell transplantations [HCTs])
- Patients must have an estimated creatinine clearance greater than 60 ml per minute by
Cockcroft-Gault formula. Serum creatinine value must be within 28 +/- 2 days prior to
registration
- Patients must have an Eastern Cooperative Oncology Group (ECOG) score =< 2 or
Karnofsky score >= 70%
- Patients must have history of CD38+ myeloma cells as demonstrated by either flow
cytometry or immunohistochemistry
- For patients of childbearing potential, must have a negative urinary pregnancy test on
the day of infusion of 211At-OKT10-B10
- Ability to provide informed consent
Exclusion Criteria:
- Patients with a history of plasma cell leukemia
- History of central nervous system involvement by multiple myeloma
- Prior radioimmunotherapy or radiation of > 20 Gy to pelvis or at maximally tolerated
levels to any critical normal organ
- Prior allogeneic hematopoietic cell transplant
- More than 2 prior autologous hematopoietic cell transplants
- Patients with medullary or extramedullary plasmacytoma/s measuring > 3 cm by magnetic
resonance imaging (MRI) or positron emission tomography (PET)-computed tomography (CT)
(radiated lesions are exempt from this criterion)
- Patients with symptomatic coronary artery disease or uncontrolled arrhythmia
- History of reactive airway disease and clinically significant asthma requiring any
form of medical treatment in the prior three months
- Left ventricular ejection fraction < 40%
- Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) < 50% 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 evidenced 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.
- Bilirubin > 2 times the upper limit of normal
- Aspartate aminotransferase [AST] and alanine aminotransferase [ALT] > 2 times the
upper limit of normal
- Patients who are known to be seropositive for human immunodeficiency virus (HIV)
- Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin
[HCG]+) or breast feeding
- Fertile men and women unwilling to use contraceptives during and for 12 months
post-transplant
- Patients with untreated and uncontrolled infection at time of enrollment
- Patients with known amyloid light-chain (AL) subtype amyloidosis
- Known allergy to murine-based monoclonal antibodies
- Known contraindications to radiotherapy
- History of another primary malignancy that has not been in remission for at least 2
years (the following are exempt from the 2-year limit: non-melanoma skin cancer,
curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy
or a squamous intraepithelial lesion on Papanicolaou [PAP] smear)
- Any anti-CD38 monoclonal antibody within 3 months of anticipated date of infusion of
211At-OKT10-B10
