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

NCT ID: NCT00477815

Last Updated: 2018-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2018-05-07

Brief Summary

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.

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab + Zevalin

Determine the dose level that is both tolerable and achieves the greatest B cell recovery in patients with multiple myeloma.

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

375 mg/m2 given as an IV infusion once weekly for four doses (days 1, 8, 15, and 22)

melphalan

Intervention Type: DRUG

100/m2 in 1000 ml 0.9% NaCI IV infusion over 1 hour daily x 2 days.

Stem Cell

Intervention Type: BIOLOGICAL

greater than or equal to 2 x 106 CD34+/kg by IV

Sargramostim (GM-CSF)

Intervention Type: BIOLOGICAL

500 mcg by Subcutaneous QD

90Y-Zevalin

Intervention Type: RADIATION

Dose escalation scheme. The dose of Zevalin will be based on the calculated radiation to the liver.

111In Zevalin

Intervention Type: BIOLOGICAL

5.0 mCi by IV

Interventions

rituximab

375 mg/m2 given as an IV infusion once weekly for four doses (days 1, 8, 15, and 22)

Intervention Type: BIOLOGICAL

melphalan

100/m2 in 1000 ml 0.9% NaCI IV infusion over 1 hour daily x 2 days.

Intervention Type: DRUG

Stem Cell

greater than or equal to 2 x 106 CD34+/kg by IV

Intervention Type: BIOLOGICAL

Sargramostim (GM-CSF)

500 mcg by Subcutaneous QD

Intervention Type: BIOLOGICAL

90Y-Zevalin

Dose escalation scheme. The dose of Zevalin will be based on the calculated radiation to the liver.

Intervention Type: RADIATION

111In Zevalin

5.0 mCi by IV

Intervention Type: BIOLOGICAL

Other Intervention Names

Rituxan, Chimeric Pan-B, C2B8, mouse-human chimeric antibody to CD20 antigen; Y2B8, 90Y-ibritumomab tiuxetan, IDEC Y2B8

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angela Dispenzieri, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC048A

Identifier Type: OTHER

Identifier Source: secondary_id

449-05

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-01399

Identifier Type: REGISTRY

Identifier Source: secondary_id

021-03-ZEV

Identifier Type: OTHER

Identifier Source: secondary_id

106-P148

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000546732

Identifier Type: -

Identifier Source: org_study_id