Fixed Dose Radioimmunotherapy (Zevalin, Yttrium-90 Ibritumomab Tiuxetan) for Patients With Incomplete Response to Chemotherapy Prior to Autologous Stem Cell Transplant for Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT01207765
First received: September 21, 2010
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: indium-111-ibritumomab tiuxetan
Drug: 90Y Zevalin
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • Safety (rate of occurrence of defined toxic events) and Efficacy (objective response rate) [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
    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%.


Secondary Outcome Measures:
  • Evaluate the kinetics of engraftment in patients who proceed to myeloablative chemotherapy after receiving 90Y Zevalin® (ibritumomab tiuxetan). [ Time Frame: Transplant through day 42 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 2 weeks prior - 2 weeks post transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 14
Study Start Date: April 2008
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01207765

Locations
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts Medical Center
Spectrum Pharmaceuticals, Inc
Investigators
Principal Investigator: Andreas K Klein, MD Tufts Medical Center
  More Information

No publications provided

Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT01207765     History of Changes
Other Study ID Numbers: Zevalin
Study First Received: September 21, 2010
Last Updated: April 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Tufts Medical Center:
Multiple Myeloma
Zevalin

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014