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| Name | Class |
|---|---|
| Spectrum Pharmaceuticals, Inc | INDUSTRY |
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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, ZevalinĀ©. ZevalinĀ© 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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 (BladƩ 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Engraftment in Patients Who Proceed to Myeloablative Chemotherapy After Receiving 90Y ZevalinĀ® (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) | Transplant through day 42 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andreas K Klein, MD | Tufts Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8649495 | Background | 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. | |
| 11806971 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Simon two-stage, min-max design test the hypothesis H0: p</=0.05 (the expected response rate for no treatment) versus Ha: p>/=0.30 (a clinically significant response rate) with a=0.05 and b=0.20.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 (BladƩ 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. | 6 subjects had objectively measurable disease and were evaluable for response, 8 subjects received study intervention and are evaluable for safety | Posted | Number | participants | Through day +104 following immunotherapy |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Septic thrombophlebitis | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| MRSA bacteremia | Infections and infestations | Systematic Assessment |
Study ended at end of stage 1
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andreas Klein, MD | Tufts Medical Center | 617-636-8884 | aklein2@tuftsmedicalcenter.org |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| C422802 | ibritumomab tiuxetan |
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| 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. |
|
| 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 +++) |
| 2 weeks prior - 2 weeks post transplant |
| 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. |
| 11924912 | 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. |
| 18172311 | 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. |
| 9753033 | 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. |
| 9816191 | 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. |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | Time to Engraftment in Patients Who Proceed to Myeloablative Chemotherapy After Receiving 90Y ZevalinĀ® (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) | Analyzed on intent-to-treat basis | Posted | Median | Full Range | Days | Transplant through day 42 |
|
|
|
| Secondary | 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 +++) | Immunohistochemical analysis showed inconsistent / insufficient CD20 staining on surface of plasma cells; comparisons could not be made | Posted | 2 weeks prior - 2 weeks post transplant |
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| 3 |
| 8 |
| 2 |
| 8 |
| Perianal absess | Infections and infestations | Systematic Assessment |
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| Myoclonus | Nervous system disorders | Systematic Assessment |
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| S. viridans bacteremia | Infections and infestations | Systematic Assessment |
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| S. epidermitis | Infections and infestations | Systematic Assessment |
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| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |