Chemotherapy, Holmium Ho 166 DOTMP, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

NCT ID: NCT00045136

Last Updated: 2009-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Holmium Ho 166 DOTMP may deliver radiation directly to cancer cells and cause less damage to normal tissue. Combining chemotherapy and holmium Ho 166 DOTMP with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and holmium Ho 166 DOTMP and kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining holmium Ho 166 DOTMP with melphalan and peripheral stem cell transplantation in treating patients who have multiple myeloma.

Detailed Description

OBJECTIVES:

• Determine the radiation absorbed dose of holmium Ho 166 DOTMP to the kidney in patients with multiple myeloma, based on whole body gamma camera image data for comparison with that obtained using an ICRP mathematical model.
• Determine the average marrow dose of this drug in these patients using gamma camera whole body counts in patients receiving this drug.
• Determine the pharmacokinetics of this drug in these patients.
• Compare marrow dose estimates determined from gamma camera whole-body counts and thyroid uptake probe counts in patients receiving this drug.
• Evaluate intra-patient variability of the uptake of this drug in the bone with repeat tests.
• Determine whether the biodistribution and dosimetry is influenced by administering this drug as a bolus compared to a 15-minute infusion in these patients.
• Compare the reduction in dose rate from the 15-minute infusion vs the bolus injection of this drug to estimate the effect on kidney exposure in these patients.
• Determine the renal transit time for each patient after bolus injection of this drug and assess whether this information improves the dose estimate to kidney with the mathematical model.
• Determine whether there is correlation of renal transit time from technetium Tc 99m-diethylenetriaminepentaacetic acid (DTPA) with holmium Ho 166 DOTMP.
• Determine the adverse events in patients receiving this drug.
• Determine the efficacy of a targeted therapy dose of holmium Ho 166 DOTMP with melphalan followed by autologous peripheral blood stem cell transplantation in these patients.

OUTLINE: This is a multicenter study. Patients are entered into one of two cohorts.

• Cohort A: Patients receive a diagnostic dose of holmium Ho 166 DOTMP IV over 15 minutes on day 1 and then IV bolus on day 8.
• Cohort B: Patients receive a diagnostic dose of holmium Ho 166 DOTMP IV over 15 minutes on days 1 and 8.

After each diagnostic dose, patients in both cohorts also undergo gamma camera imaging of the whole body on days 1 and 8.

Approximately 1-3 weeks later, patients in both cohorts who demonstrate adequate uptake of the first diagnostic dose of holmium Ho 166 DOTMP into the bone marrow then receive therapeutic holmium Ho 166 DOTMP IV over 15 minutes once between days -13 to -10 followed by melphalan IV over 20-30 minutes once between days -10 to -1. Patients undergo autologous peripheral blood stem cell transplantation on day 0.

Patients are followed monthly for 1 year and then every 3 months for 1 year.

PROJECTED ACCRUAL: A minimum of 12 patients (6 per cohort) will be accrued for this study.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Study Design

• Primary Study Purpose: TREATMENT

Interventions

melphalan

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

holmium Ho 166 DOTMP

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• No non-secretory MM
• No symptomatic MGUS, smoldering MM, or indolent MM
• No solitary bone or extramedullary plasmacytoma
• No immunoglobulin M myeloma
• Prior induction therapy for myeloma required
• Responding, stable, or progressive disease after induction therapy, or relapsed disease
• Candidate for autologous hematopoietic stem cell transplantation
• Prior stem cell mobilization with chemotherapy and growth factors according to institutional procedures

• Availability of at least 2,000,000 CD34+ cells/kg

PATIENT CHARACTERISTICS:

Age

• 18 to 70

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2 mg/dL
• SGPT no greater than 2 times upper limit of normal
• No clinical evidence of amyloidosis of the liver

Renal

• Creatinine no greater than 2.0 mg/dL
• Creatinine clearance at least 45 mL/min
• Renal ultrasound normal
• No clinical evidence of amyloidosis of the kidney
• No urinary obstruction in the renal pelvis, ureter, or bladder outlet by ultrasound

Cardiovascular

• Ejection fraction at least 50% with no evidence of amyloidosis by echocardiogram
• No clinical evidence of amyloidosis of the heart
• No uncontrolled arrhythmia
• No symptomatic cardiac disease

Pulmonary

• FEV1, FVC, and DLCO at least 60%
• No symptomatic pulmonary disease
• No clinical evidence of amyloidosis of the lungs

Other

• No known allergy to vitamin C or bisphosphonates
• No known hypersensitivity to technetium Tc 99m phosphorus radiopharmaceuticals (e.g., technetium Tc 99m-methylene diphosphonate)
• No concurrent illness that would severely limit life expectancy
• No symptoms, physical findings, or radiographic evidence of cord compression
• No clinical evidence of amyloidosis of the autonomic nervous system or gastrointestinal tract
• No prior noncompliance in other studies
• No other malignancy within the past 5 years except treated indolent skin cancers or carcinoma in situ of the cervix
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior stem cell or bone marrow transplantation
• No concurrent maintenance therapy comprising interferon or thalidomide

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• See Disease Characteristics
• No concurrent maintenance therapy comprising dexamethasone

Radiotherapy

• No prior cumulative external-beam radiotherapy (EBRT) to more than 20% of bone marrow
• No prior cumulative EBRT dose of 30 Gy or more to the spinal cord
• No prior radiotherapy to the bladder

Surgery

• See Disease Characteristics

Other

• At least 4 weeks since prior investigational agents for MM
• At least 4 weeks since other prior experimental therapies for any other condition
• No bisphosphonates for at least 4 weeks before study, during study, and for at least 30 days posttransplantation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Poniard Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Principal Investigators

Wendy Jenkins

Role: PRINCIPAL_INVESTIGATOR

Poniard Pharmaceuticals

Locations

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

University of California Davis Cancer Center

Sacramento, California, United States

Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus

Nashville, Tennessee, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

PONIARD-0102

Identifier Type: -

Identifier Source: secondary_id

NEORX-0102

Identifier Type: -

Identifier Source: secondary_id

FHCRC-1704.00

Identifier Type: -

Identifier Source: secondary_id

CDR0000256377

Identifier Type: -

Identifier Source: org_study_id