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

Mayo Clinic

Status and phase

Completed

Phase 1

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Treatments

Biological: Stem Cell

Biological: Sargramostim (GM-CSF)

Drug: melphalan

Biological: 111In Zevalin

Biological: rituximab

Radiation: 90Y-Zevalin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00477815

P30CA015083 (U.S. NIH Grant/Contract)

MC048A (Other Identifier)

CDR0000546732

106-P148 (Other Identifier)

NCI-2009-01399 (Registry Identifier)

021-03-ZEV (Other Identifier)

449-05 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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