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

NCT01207765 | Terminated Phase 2 Results

• 1 other identifier: Zevalin
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Zevalin

Outcome Measures

Primary Outcomes (1)

• 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.

  Through day +104 following immunotherapy

Secondary Outcomes (2)

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

  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

  2 weeks prior - 2 weeks post transplant

Study Arms (1)

Zevalin

EXPERIMENTAL

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; Drug: 90Y Zevalin

Interventions

indium-111-ibritumomab tiuxetan DRUG

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.

Also known as: 111 In Zevalin

Zevalin

90Y Zevalin DRUG

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.

Zevalin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Tufts Medical Center: lead
• Spectrum Pharmaceuticals, Inc: collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (6)

• 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.

  PMID: 8649495 BACKGROUND

• 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.

  PMID: 11806971 BACKGROUND

• 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.

  PMID: 11924912 BACKGROUND

• 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.

  PMID: 18172311 BACKGROUND

• 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.

  PMID: 9753033 BACKGROUND

• 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.

  PMID: 9816191 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Study ended at end of stage 1

Results Point of Contact

• Title: Andreas Klein, MD
• Organization: Tufts Medical Center

aklein2@tuftsmedicalcenter.org

617-636-8884

Study Officials

• Andreas K Klein, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: September 23, 2010
• Study Start: April 1, 2008
• Primary Completion: January 1, 2013
• Study Completion: June 1, 2013
• Last Updated: March 20, 2017
• Results First Posted: October 28, 2016

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)