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Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan, Melphalan, and Autologous Peripheral Stem Cell Transplant in Treating Patients With Previously Treated Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00477815
First received: May 23, 2007
Last updated: March 24, 2014
Last verified: March 2014

May 23, 2007
March 24, 2014
May 2005
September 2014   (final data collection date for primary outcome measure)
  • Toxicity as measured by CTCAE v 3.0 [ Time Frame: 19 Months ] [ Designated as safety issue: Yes ]
  • Clonotypic B cells [ Time Frame: 19 months ] [ Designated as safety issue: No ]
  • Toxicity as measured by CTCAE v 3.0
  • Clonotypic B cells
Complete list of historical versions of study NCT00477815 on ClinicalTrials.gov Archive Site
  • Response (complete response, very good partial response, partial response) [ Time Frame: 19 months ] [ Designated as safety issue: No ]
  • Time to progression and duration of response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Impact of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonal plasma cells in the blood and marrow prior to high-dose melphalan [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • Response (complete response, very good partial response, partial response)
  • Time to progression and duration of response
  • Impact of the rituximab and yttrium Y 90 ibritumomab tiuxetan component of treatment on the clonal plasma cells in the blood and marrow prior to high-dose melphalan
Not Provided
Not Provided
 
Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan, Melphalan, and Autologous Peripheral Stem Cell Transplant in Treating Patients With Previously Treated Multiple Myeloma
A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving monoclonal antibody therapy together with chemotherapy and autologous peripheral stem cell transplant may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of yttrium Y 90 ibritumomab tiuxetan when given together with rituximab, melphalan, and autologous peripheral stem cell transplant in treating patients with previously treated multiple myeloma.

OBJECTIVES:

Primary

  • Determine the safety of rituximab, yttrium Y 90 ibritumomab tiuxetan, high-dose melphalan, and autologous peripheral blood stem cell transplantation in patients with previously treated multiple myeloma.
  • Determine the effect of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonotypic B-cells at baseline and at B-cell recovery in these patients.

Secondary

  • Determine the response rate and progression factors (time to progression, progression-free survival, and duration of response) in patients treated with this regimen.
  • Determine the effect of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonal plasma cells in the blood and marrow prior to high-dose melphalan.

OUTLINE: This is a dose-escalation study of yttrium Y 90 ibritumomab tiuxetan.

Patients receive rituximab IV followed by a dosimetry dose of indium In 111 ibritumomab tiuxetan IV over 10 minutes on day -22. Patients with acceptable biodistribution receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14, high-dose melphalan IV over 1 hour on days -2 and -1, and undergo autologous peripheral blood stem cell transplantation on day 0. Patients also receive sargramostim (GM-CSF) subcutaneously beginning on day 0 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of yttrium Y 90 ibritumomab tiuxetan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Bone marrow, blood, and urine samples are collected at baseline and then periodically during study for biomarker correlative studies.

After completion of study treatment, patients are followed every 3 months for 5 years.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma and Plasma Cell Neoplasm
  • Biological: rituximab
    375 mg/m2 given as an IV infusion once weekly for four doses (days 1, 8, 15, and 22)
    Other Name: Rituxan, Chimeric Pan-B, C2B8, mouse-human chimeric antibody to CD20 antigen
  • Drug: melphalan
    100/m2 in 1000 ml 0.9% NaCI IV infusion over 1 hour daily x 2 days.
  • Biological: Stem Cell
    greater than or equal to 2 x 106 CD34+/kg by IV
  • Biological: Sargramostim (GM-CSF)
    500 mcg by Subcutaneous QD
  • Radiation: 90Y-Zevalin
    Dose escalation scheme. The dose of Zevalin will be based on the calculated radiation to the liver.
    Other Name: Y2B8, 90Y-ibritumomab tiuxetan, IDEC Y2B8
  • Biological: 111In Zevalin
    5.0 mCi by IV
Experimental: Rituximab + Zevalin
Determine the dose level that is both tolerable and achieves the greatest B cell recovery in patients with multiple myeloma.
Interventions:
  • Biological: rituximab
  • Drug: melphalan
  • Biological: Stem Cell
  • Biological: Sargramostim (GM-CSF)
  • Radiation: 90Y-Zevalin
  • Biological: 111In Zevalin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
42
Not Provided
September 2014   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma

    • Previously treated disease
  • Candidate for high-dose chemotherapy with melphalan and autologous stem cell transplantation
  • No definite evidence of myelodysplasia on pretreatment bone marrow by morphology or by chromosome analysis (e.g., monosomy 7)

    • Chromosome abnormalities from the myeloma clone allowed

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 2.0 mg/dL
  • Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN
  • Creatinine ≤ 2 times ULN
  • LVEF ≥ 45%
  • Corrected pulmonary diffusion capacity ≥ 50%
  • No uncontrolled infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other active malignancy (with the exception of nonmelanoma skin cancer) that requires myelosuppressive chemotherapy or radiation therapy
  • No HIV positivity

PRIOR CONCURRENT THERAPY:

  • More than 3 weeks since prior myelosuppressive chemotherapy, except cyclophosphamide pulsing for stem cell collection)
  • No other concurrent immunotherapy, radiotherapy, chemotherapy or antimyeloma therapy
  • Concurrent chronic corticosteroids at doses of prednisone ≤ 20 mg per day (or equivalent) allowed
  • Concurrent adjuvant hormonal therapy (e.g., tamoxifen citrate or leuprolide acetate) allowed
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00477815
CDR0000546732, P30CA015083, MC048A, 449-05, NCI-2009-01399, 021-03-ZEV, 106-P148
Yes
Angela Dispenzieri, M.D., Mayo Clinic Cancer Center
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Angela Dispenzieri, MD Mayo Clinic
Mayo Clinic
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP