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

Primary Purpose

Multiple Myeloma

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

indium-111-ibritumomab tiuxetan

90Y Zevalin

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Zevalin

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Tufts Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zevalin

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety and Efficacy

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.

Secondary Outcome Measures

Time to Engraftment in Patients Who Proceed to Myeloablative Chemotherapy After Receiving 90Y Zevalin® (Ibritumomab Tiuxetan).

Number of days from stem cell infusion (day +0) to day of neutrophil engraftment (first of three consecutive days with absolute neutrophil count > 500)

Degree of CD20 Expression on Plasma Cells and/or Targeting of Post-germinal Center B Cells Correlation With Toxicity, Response and Biodistribution

CD20 immunohistochemical staining of plasma cells on baseline bone marrow biopsy specimen, graded on qualitative scale (0 to +++)

Full Information

NCT ID

NCT01207765

First Posted

September 21, 2010

Last Updated

February 10, 2017

Sponsor

Tufts Medical Center

Collaborators

Spectrum Pharmaceuticals, Inc

1. Study Identification

Unique Protocol Identification Number

NCT01207765

Brief Title

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

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Terminated

Why Stopped

changes in practice

Study Start Date

April 2008 (undefined)

Primary Completion Date

January 2013 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tufts Medical Center

Collaborators

Spectrum Pharmaceuticals, Inc

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

Multiple Myeloma, Zevalin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Zevalin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

indium-111-ibritumomab tiuxetan

Other Intervention Name(s)

111 In Zevalin

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

90Y Zevalin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety and Efficacy

Description

Time Frame

Through day +104 following immunotherapy

Secondary Outcome Measure Information:

Title

Time to Engraftment in Patients Who Proceed to Myeloablative Chemotherapy After Receiving 90Y Zevalin® (Ibritumomab Tiuxetan).

Description

Number of days from stem cell infusion (day +0) to day of neutrophil engraftment (first of three consecutive days with absolute neutrophil count > 500)

Time Frame

Transplant through day 42

Title

Degree of CD20 Expression on Plasma Cells and/or Targeting of Post-germinal Center B Cells Correlation With Toxicity, Response and Biodistribution

Description

CD20 immunohistochemical staining of plasma cells on baseline bone marrow biopsy specimen, graded on qualitative scale (0 to +++)

Time Frame

2 weeks prior - 2 weeks post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andreas K Klein, MD

Organizational Affiliation

Tufts Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Tufts Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

8649495

Citation

Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996 Jul 11;335(2):91-7. doi: 10.1056/NEJM199607113350204.

Results Reference

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PubMed Identifier

11806971

Citation

Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ, Guilhot F, Marit G, Doyen C, Jaubert J, Fuzibet JG, Francois S, Benboubker L, Monconduit M, Voillat L, Macro M, Berthou C, Dorvaux V, Pignon B, Rio B, Matthes T, Casassus P, Caillot D, Najman N, Grosbois B, Bataille R, Harousseau JL; Intergroupe Francophone du Myelome. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood. 2002 Feb 1;99(3):731-5. doi: 10.1182/blood.v99.3.731.

Results Reference

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PubMed Identifier

11924912

Citation

Treon SP, Pilarski LM, Belch AR, Kelliher A, Preffer FI, Shima Y, Mitsiades CS, Mitsiades NS, Szczepek AJ, Ellman L, Harmon D, Grossbard ML, Anderson KC. CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications. J Immunother. 2002 Jan-Feb;25(1):72-81. doi: 10.1097/00002371-200201000-00008.

Results Reference

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PubMed Identifier

18172311

Citation

Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, McNiece I, Lin L, Ambinder RF, Peacock C, Watkins DN, Huff CA, Jones RJ. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008 Jan 1;68(1):190-7. doi: 10.1158/0008-5472.CAN-07-3096.

Results Reference

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PubMed Identifier

9753033

Citation

Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998 Sep;102(5):1115-23. doi: 10.1046/j.1365-2141.1998.00930.x. No abstract available.

Results Reference

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PubMed Identifier

9816191

Citation

Knox SJ, Goris ML, Trisler K, Negrin R, Davis T, Liles TM, Grillo-Lopez A, Chinn P, Varns C, Ning SC, Fowler S, Deb N, Becker M, Marquez C, Levy R. Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. Clin Cancer Res. 1996 Mar;2(3):457-70.

Results Reference

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

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