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

NCT00477815 | Completed Phase 1 DMC

• 7 other identifiers: CDR0000546732P30CA015083MC048A449-05NCI-2009-01399021-03-ZEV106-P148
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage I multiple myeloma; refractory multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (2)

• Toxicity as measured by CTCAE v 3.0

  19 Months

• Clonotypic B cells

  19 months

Secondary Outcomes (3)

• Response (complete response, very good partial response, partial response)

  19 months

• Time to progression and duration of response

  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

  1 week

Study Arms (1)

Rituximab + Zevalin

EXPERIMENTAL

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

Biological: rituximab; Drug: melphalan; Biological: Stem Cell; Biological: Sargramostim (GM-CSF); Radiation: 90Y-Zevalin; Biological: 111In Zevalin

Interventions

rituximab BIOLOGICAL

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

Also known as: Rituxan, Chimeric Pan-B, C2B8, mouse-human chimeric antibody to CD20 antigen

Rituximab + Zevalin

melphalan DRUG

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

Rituximab + Zevalin

Stem Cell BIOLOGICAL

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

Rituximab + Zevalin

Sargramostim (GM-CSF) BIOLOGICAL

500 mcg by Subcutaneous QD

Rituximab + Zevalin

90Y-Zevalin RADIATION

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

Also known as: Y2B8, 90Y-ibritumomab tiuxetan, IDEC Y2B8

Rituximab + Zevalin

111In Zevalin BIOLOGICAL

5.0 mCi by IV

Rituximab + Zevalin

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Rituximab; Melphalan; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Angela Dispenzieri, MD

  Mayo Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2007
• First Posted: May 24, 2007
• Study Start: May 31, 2005
• Primary Completion: July 28, 2011
• Study Completion: May 7, 2018
• Last Updated: May 14, 2018

Record last verified: 2018-05

Locations

US (1)