Fixed Dose Radioimmunotherapy (Zevalin) for Patients With Incomplete Response to Chemo Prior to Autologous Stem Cell Transplant for Multiple Myeloma

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01207765
• Other study ID #: Zevalin
• Status: Completed
• Phase: Phase 2
• First received: September 21, 2010
• Last updated: December 8, 2014
• Start date: April 2008
• Est. completion date: June 2013

Study information

• Verified date: December 2014
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

Patients with multiple myeloma measurable disease following stem cell mobilization with institution standard high dose cyclophosphamide and 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: June 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• indium-111-ibritumomab tiuxetan
1.5mg of 111In Zevalin (containing 5 mCi of 111In) will be used for radioimaging. 111In Zevalin will be administered by a 10 minute slow IV push injection immediately following completion of the rituximab infusion. 111In Zevalin may be injected by stopping the flow from the IV bag and injecting the radiolabeled antibody directly into the IV line. A 0.22 micron filter must be on line between the drug infusion port and the patient. The line must be flushed with at least 10cc of normal saline after 111In Zevalin has been injected.
• 90Y Zevalin
Each patient will receive a single therapeutic dose of 90Y Zevalin at a dose of 0.4 mCi/kg, capped at a maximum dose of 32 mCi. 90Y Zevalin will be administered intravenously as a slow IV push over 10 minutes. 90Y Zevalin may be directly infused by stopping the flow from the IV bag and injecting the radiolabeled antibody directly into the IV line. A 0.22 micron filter must be on line between the syringe and the infusion port. The line must be flushed with at least 10cc normal saline after 90Y Zevalin has been infused.

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Tufts Medical Center	Spectrum Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (rate of occurrence of defined toxic events) and Efficacy (objective response rate)	For efficacy, the objective response rate (CR + PR) at 12 and 104 days following radioimmunotherapy will be determined. For safety, the rate of occurrence of defined toxic events including non-engraftment and unacceptable biodistribution of 90Y Zevalin occurring by day +42 following transplant will be determined. The intervention will be considered safe if the rate of toxic events is less than 20%.	Throughout the study	Yes
Secondary	Evaluate the kinetics of engraftment in patients who proceed to myeloablative chemotherapy after receiving 90Y Zevalin® (ibritumomab tiuxetan).		Transplant through day 42	No
Secondary	Evaluate whether the degree of CD20 expression on plasma cells and/or targeting of post-germinal center B cells correlate with toxicity, response, biodistribution and other clinical parameters.		2 weeks prior - 2 weeks post transplant	No