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

May 8, 2018 updated by: Mayo Clinic

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Y2B8, 90Y-ibritumomab tiuxetan, IDEC Y2B8
Biological: 111In Zevalin
5.0 mCi by IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Toxicity as measured by CTCAE v 3.0
Time Frame: 19 Months
19 Months
Clonotypic B cells
Time Frame: 19 months
19 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Response (complete response, very good partial response, partial response)
Time Frame: 19 months
19 months
Time to progression and duration of response
Time Frame: 5 years
5 years
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
1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 31, 2005

Primary Completion (ACTUAL)

July 28, 2011

Study Completion (ACTUAL)

May 7, 2018

Study Registration Dates

First Submitted

May 23, 2007

First Submitted That Met QC Criteria

May 23, 2007

First Posted (ESTIMATE)

May 24, 2007

Study Record Updates

Last Update Posted (ACTUAL)

May 14, 2018

Last Update Submitted That Met QC Criteria

May 8, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000546732
  • P30CA015083 (U.S. NIH Grant/Contract)
  • MC048A (OTHER: Mayo Clinic Cancer Center)
  • 449-05 (OTHER: Mayo Clinic IRB)
  • NCI-2009-01399 (REGISTRY: NCI-CTRO)
  • 021-03-ZEV (OTHER: Biogen IDEC protocol)
  • 106-P148 (OTHER: Biogen IDEC protocol)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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