Clinical Trial of Consolidation Treatment With Iodine I 131 Tositumomab for Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00135200
First received: August 24, 2005
Last updated: August 29, 2013
Last verified: August 2013
  Purpose

This study is for patients with newly diagnosed or relapsed multiple myeloma. The main purpose of this study is to see how their disease responds to consolidation treatment (treatment aimed at further decreasing cancer cells) with a radioactive antibody (protein) called iodine I 131 tositumomab (known by the tradename Bexxar®) and also to look at the side effects which occur with this type of treatment. The investigators will also be looking at how long disease responds to treatment, if it responds at all, and how long patients who have had this treatment survive.

Bexxar is a monoclonal antibody (protein) to which radioactive iodine 131 is attached. The monoclonal antibody in Bexxar (tositumomab), targets a protein called CD20 found on the surface of a variety of B-cells, including lymphoma cells, and some myeloma cells. The antibody is given as an infusion and finds its way to these cells. The radioactive iodine attached to the antibody delivers radiation directly to these cells which works to harm or kill the cancer cells. Approximately 20-25% of patients with multiple myeloma have this protein on the surface of their tumor cells. In addition, this protein was found on the surface of myeloma stem cells. While myeloma stem cells represent a minority of all myeloma cells (less than 5%), these cells are resistant to chemotherapy and are believed to be responsible for a recurrence of the disease after chemotherapy. In this study, Bexxar will be used after patients complete a course of chemotherapy and have residual myeloma cells left in their body. The Investigators are hoping that the treatment with Bexxar will decrease and possibly eliminate residual myeloma cells resistant to chemotherapy.


Condition Intervention Phase
Multiple Myeloma
Drug: Iodine I 131 Tositumomab
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial of Consolidation Treatment With Iodine I 131 Tositumomab for Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Determination of the rate of additional cytoreduction after treatment with Bexxar (defined as sustained reduction of monoclonal proteins by more than 25% versus pre-Bexxar level) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determination of the rate of conversion to complete response (CR) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Estimate of duration of response, progression-free survival, and time to treatment failure [ Time Frame: 3-6 months ] [ Designated as safety issue: Yes ]
  • Estimate of quantity and quality (measured by the rate of engraftment) of stem cell collections [ Time Frame: 3-6 months ] [ Designated as safety issue: Yes ]
  • Estimate of the efficacy of elimination of clonogenic myeloma cells [ Time Frame: 3-6 months ] [ Designated as safety issue: Yes ]
  • Determination of the safety and tolerability of consolidation therapy with Bexxar, as determined by the incidence of clinical and laboratory toxicities [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: August 2005
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bexxar therapeutic
The Bexxar therapeutic regimen is delivered in two sets of intravenous infusions given 7-14 days apart. Nonradioactive Tositumomab is given before both the "dosimetric" infusion and the "therapeutic" infusion to improve distribution of these doses throughout the body. A trace amount of radioactive Iodine 131 Tositumomab is initially given to enable physicians to evaluate the clearance of radiation from the subject's body with gamma camera scans. Calculations made on the basis of these individualized radiation clearance rates allow the therapeutic dose (given 7-14 days after the dosimetric infusion) to be tailored for each patient. The therapeutic dose contains Tositumomab labeled with the amount of Iodine 131 tositumomab specifically calculated based on the scans performed following the dosimetric dose.
Drug: Iodine I 131 Tositumomab
The Bexxar therapeutic regimen is delivered in two sets of intravenous infusions given 7-14 days apart. Nonradioactive Tositumomab is given before both the "dosimetric" infusion and the "therapeutic" infusion to improve distribution of these doses throughout the body. A trace amount of radioactive Iodine 131 attached to Tositumomab is initially given to enable physicians to evaluate the clearance of radiation from your body with gamma camera scans. Calculations made on the basis of these individualized radiation clearance rates allow the therapeutic dose (given 7-14 days after the dosimetric infusion) to be tailored for each patient. The therapeutic dose contains Tositumomab labeled with the amount of Iodine 131 tositumomab specifically calculated for you based on the scans performed following the dosimetric dose.
Other Name: Bexxar

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • Expected survival ≥ 6 months
  • Pre-study performance status of 0, 1, or 2 according to the World Health Organization (WHO)
  • Newly diagnosed or relapsed/refractory myeloma with histologic confirmation of multiple myeloma by the Department of Pathology at University of Michigan Cancer Center (UMCC)
  • Not more than 3 lines of therapy for myeloma for patients with relapsed disease
  • Documented Stage II or III multiple myeloma (Durie and Salmon, 1975) prior to initiation of first line therapy
  • At least 4 cycles of first line (for newly diagnosed patients) or salvage (for relapsed/refractory patients) prior therapy and in a plateau of at least partial response (Blade et al, 1999) for at least 2 determinations 6 weeks apart
  • At least 21 days from day 1 of the last cycle and fully recovered from all toxicities associated with prior surgery, radiation treatments, chemotherapy, or immunotherapy
  • Measurable M-proteins with greater than 1 g/dl serum monoclonal protein and/or greater than 0.5 g/24 hour urine light chain excretion
  • Acceptable hematologic status within two weeks prior to patient registration, including:

    • Absolute neutrophil count ([segmented neutrophils + bands] x total white blood cell [WBC]) ≥ 1,500/mm3;
    • Platelet counts ≥ 150,000/mm3; these patients will receive total body dose of 75 cGy of Bexxar; or
    • Platelet counts from 100,000/mm3 to 149,000/mm3; these patients will receive a 65 cGy total body dose of Bexxar;
    • In patients previously treated with ASCT, total body dose will be 55 cGy in patients with platelet count > 150,000 and 45 cGy in patients with platelets 100,000-149,000.
  • Female patients who are not pregnant or lactating
  • Men and women of reproductive potential who are following accepted birth control methods (as determined by the treating physician)
  • Patients previously on Phase II drugs if no long-term toxicity is expected, and the patient has been off the drug for three or more weeks with no significant post treatment toxicities observed
  • Patients determined to have < 25% bone marrow involvement with myeloma within six weeks of registration (based on bilateral core biopsy).

Exclusion Criteria:

  • Patients with impaired bone marrow reserve, as indicated by one or more of the following:

    • Platelet count < 100,000 cells/mm3;
    • Hypocellular bone marrow;
    • Marked reduction in bone marrow precursors of one or more cell lines (granulocytic, megakaryocytic, erythroid);
    • History of failed stem cell collection;
    • Myelodysplastic syndrome (MDS) or evidence of other than myeloma clonogenic abnormalities;
    • Prior radioimmunotherapy;
    • Prior anti-CD20 therapy;
    • Other than myeloma malignancy, except B-cell non-Hodgkin's lymphoma, basal and squamous cell carcinoma of the skin, and cervical and breast cancer in situ, unless patient is cancer free for > 3 years;
    • Central nervous system (CNS) involvement;
    • Patients with known HIV infection;
    • Patients with pleural effusion;
    • Patients with abnormal liver function: total bilirubin > 2.0 mg/dL;
    • Patients with abnormal renal function: serum creatinine > 2.0 mg/dL;
    • Patients who have received prior external beam radiation therapy to > 25% of active bone marrow (involved field or regional);
    • Patients who have received G-CSF or GM-CSF therapy within two weeks prior to treatment;
    • Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives;
    • Major surgery, other than diagnostic surgery, within four weeks;
    • Presence of anti-murine antibody (HAMA) reactivity. This result must be available prior to receiving treatment for those patients with prior exposure to murine antibodies or proteins.
  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: NCT00135200

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
GlaxoSmithKline
Investigators
Principal Investigator: Mark Kaminski, MD University of Michigan
  More Information

No publications provided

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00135200     History of Changes
Other Study ID Numbers: UMCC 2005.035, IRB # 2005-0403 and HUM 43767
Study First Received: August 24, 2005
Last Updated: August 29, 2013
Health Authority: United States: Institutional Review Board

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
Iodine
Iodine-131 anti-B1 antibody
Antibodies, Monoclonal
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on October 02, 2014