Zevalin for Patients With Incomplete Response to Chemo Prior to Autologous Stem Cell Transplant for Multiple Myeloma
Zevalin for Patients With Incomplete Response to Chemo Prior to Autologous Stem Cell Transplant for Multiple Myeloma
The study involves the use of a targeted form of radiation, in addition to standard high dose
 chemotherapy and stem cell transplant for multiple myeloma. The use of targeted radiation is
 designed to kill more multiple myeloma cells while avoiding the side effects of standard
 radiation. This type of targeted radiation (also known as radioimmunotherapy) has been
 approved by the Food and Drug Administration (FDA) for the treatment of a related disease,
 lymphoma under the trade name, Zevalin©. Zevalin© has been added to high dose chemotherapy
 and stem cell transplants for patients with lymphoma and is now being studied in this
 clinical trial for patients with multiple myeloma. This trial is only available at Tufts
 Medical Center.

 The proposed clinical trial will test whether CD20-targeted radio-immunotherapy can be safe
 and effective when integrated into a standard regimen of myeloablative chemotherapy and
 autologous stem cell rescue in patients with measurable disease prior to high dose
 chemotherapy and autologous stem cell transplant for multiple myeloma.
Patients with multiple myeloma scheduled for standard of care high dose melphalan and
 autologous stem cell transplant who have an incomplete response to induction treatment (i.e.
 with measurable disease) following peripheral blood stem cell collection are candidates for
 participation on this trial. 90Y Zevalin targets CD20 expressed on the surface of mature
 B-cells and is FDA approved for relapsed/refractory low grade lymphoma. This is a single arm,
 phase II safety and efficacy study of 90-Y Zevalin in multiple myeloma. Subjects will receive
 cold antibody (Rituximab 100mg/m2) followed by 5 mCi test dose of 111-In Zevalin on
 transplant day -21. Gamma camera images are obtained 48 to 72 hours after 111-In Zevalin to
 document appropriate / expected distribution of radiotracer. On transplant day -14, subjects
 will receive another cold antibody dose followed by 90Y Zevalin 0.4 mg/kg (max 32 mCi) as
 single dose. Subjects are admitted for transplant on day -3 and proceed with institution
 standard high dose melphalan (200mg/m2) on day -2. Subjects are followed for safety for 6
 weeks after transplant.
Inclusion Criteria:

 -  Meet established criteria for the diagnosis of multiple myeloma

 -  Durie-Salmon stage II or III disease

 -  Measurable disease in the serum and/or urine

 -  Scheduled to receive high dose chemotherapy and autologous stem cell transplant for
 multiple myeloma

 -  Individuals who have previously undergone autologous stem cell transplant are eligible
 for this study provided more than 6 months have elapsed from the prior transplant.

 -  Minimum stem cell dose of 4x106 CD34+ MNC / kg stored for autologous stem cell rescue.

 -  Adequate hematologic reserve as evidenced by ANC ≥ 1500/mm3 and platelets ≥
 100,000/mm3.

 -  Serum direct bilirubin ≤ 2.0 mg/dl and transaminases ≤ 3x institution upper limit of
 normal.

 -  Serum creatinine ≤ 2 mg/dl with creatinine clearance ≥ 60 ml/min (either calculated or
 measured).

 Exclusion Criteria:

 -  Stage I or smoldering myeloma, isolated plasmacytoma, or benign monoclonal gammopathy

 -  Non-secretory multiple myeloma

 -  Pregnant or lactating women

 -  Males and females who do not agree to practice approved methods of birth control for
 the duration of the study

 -  Presence of active infection

 -  Receipt of previous radiation therapy to critical organs exceeding any of the
 following limits: kidney 500 cGy, liver 1000 cGy, lungs 500 cGy