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
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: rituximab
Drug: melphalan
Biological: Stem Cell
Biological: Sargramostim (GM-CSF)
Radiation: 90Y-Zevalin
Biological: 111In Zevalin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 42
Study Start Date: May 2005
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab + Zevalin
Determine the dose level that is both tolerable and achieves the greatest B cell recovery in patients with multiple myeloma.
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

Detailed Description:

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.

  Eligibility

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

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
  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: NCT00477815

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Angela Dispenzieri, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Angela Dispenzieri, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00477815     History of Changes
Other Study ID Numbers: CDR0000546732, P30CA015083, MC048A, 449-05, NCI-2009-01399, 021-03-ZEV, 106-P148
Study First Received: May 23, 2007
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
stage I multiple myeloma
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Rituximab
Antibodies, Monoclonal
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 31, 2014