Clinical trial NCT01207765: Zevalin for Patients With Incomplete Response to Chemo Prior to Autologous Stem Cell Transplant for Multiple Myeloma
Official title: A Phase II, Safety and Efficacy Study of Fixed Dose Radioimmunotherapy (Zevalin, Yttrium-90 Ibritumomab Tiuxetan) for Patients With Incomplete Response to Chemotherapy Prior to Autologous Stem Cell Transplant for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Zevalin
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
Collaborators: name: Spectrum Pharmaceuticals, Inc
First posted: 2010-09-23
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Efficacy
timeFrame: Through day +104 following immunotherapy
Secondary outcomes:
measure: Time to Engraftment in Patients Who Proceed to Myeloablative Chemotherapy After Receiving 90Y Zevalin® (Ibritumomab Tiuxetan).
timeFrame: Transplant through day 42
measure: Degree of CD20 Expression on Plasma Cells and/or Targeting of Post-germinal Center B Cells Correlation With Toxicity, Response and Biodistribution
timeFrame: 2 weeks prior - 2 weeks post transplant
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center
name: Andreas K Klein, MD
role: PRINCIPAL_INVESTIGATOR
References:
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