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

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

A Phase I Trial of Zevalin Radioimmunotherapy With High-Dose Melphalan and Stem Cell Transplant for Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00477815
• Other study ID #: CDR0000546732
• Secondary ID: P30CA015083MC048
• Status: Completed
• Phase: Phase 1
• Start date: May 31, 2005
• Est. completion date: May 7, 2018

Study information

• Verified date: May 2018
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: May 7, 2018
• Est. primary completion date: July 28, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

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

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
• 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.

Biological:
• 111In Zevalin
5.0 mCi by IV

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity as measured by CTCAE v 3.0		19 Months
Primary	Clonotypic B cells		19 months
Secondary	Response (complete response, very good partial response, partial response)		19 months
Secondary	Time to progression and duration of response		5 years
Secondary	Impact of rituximab and yttrium Y 90 ibritumomab tiuxetan on the clonal plasma cells in the blood and marrow prior to high-dose melphalan		1 week