Zevalin for Patients With Incomplete Response to Chemo Prior to Autologous Stem Cell Transplant for Multiple Myeloma

February 10, 2017 updated by: Tufts Medical Center

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zevalin
1.5mg of 111In Zevalin (containing 5 mCi of 111In) will be used for radioimaging on study day +1. 90Y Zevalin will be administered seven to nine days after 111In Zevalin administration. The dose of 90Y Zevalin will be 0.4 mCi/kg, capped at a maximum dose of 32 mCi.
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.
Other Names:
  • 111 In Zevalin
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Efficacy
Time Frame: Through day +104 following immunotherapy
Efficacy: objective response rate (CR + PR) at 12 and 104 days following radioimmunotherapy. Safety: the rate of occurrence of defined toxic events including non-engraftment and unacceptable biodistribution of 90Y Zevalin occurring by day +42 following transplant. Response determined according to Blade' Criteria (Bladé J, Br J Haematol.1998 Sep;102(5):1115-23) for multiple myeloma; Response based on reduction of monoclonal protein (M-protein) from initial presentation.
Through day +104 following immunotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Engraftment in Patients Who Proceed to Myeloablative Chemotherapy After Receiving 90Y Zevalin® (Ibritumomab Tiuxetan).
Time Frame: Transplant through day 42
Number of days from stem cell infusion (day +0) to day of neutrophil engraftment (first of three consecutive days with absolute neutrophil count > 500)
Transplant through day 42
Degree of CD20 Expression on Plasma Cells and/or Targeting of Post-germinal Center B Cells Correlation With Toxicity, Response and Biodistribution
Time Frame: 2 weeks prior - 2 weeks post transplant
CD20 immunohistochemical staining of plasma cells on baseline bone marrow biopsy specimen, graded on qualitative scale (0 to +++)
2 weeks prior - 2 weeks post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tufts Medical Center

Collaborators

Spectrum Pharmaceuticals, Inc

Investigators

  • Principal Investigator: Andreas K Klein, MD, Tufts Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

June 1, 2013

Study Registration Dates

First Submitted

September 21, 2010

First Submitted That Met QC Criteria

September 22, 2010

First Posted (Estimate)

September 23, 2010

Study Record Updates

Last Update Posted (Actual)

March 20, 2017

Last Update Submitted That Met QC Criteria

February 10, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Zevalin

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Study Data/Documents

  1. Biology of Blood and Marrow Transplant , Volume 21 , Issue 2 , S199
    Information comments: Published Abstract

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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