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

This study has been completed.
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: September 6, 2002
Last updated: April 2, 2009
Last verified: April 2009

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.

Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: melphalan
Procedure: peripheral blood stem cell transplantation
Radiation: holmium Ho 166 DOTMP
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Multicenter Dosimetry Trial to Evaluate Radiation Absorbed Dose From Holmium-166-DOTMP in Patients With Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: January 2002
Primary Completion Date: January 2003 (Final data collection date for primary outcome measure)
Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of multiple myeloma (MM)

    • Patients with a prior diagnosis of monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma are eligible if they progressed and met the criteria for diagnosis of MM
  • 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



  • 18 to 70

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Not specified


  • 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


  • 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


  • 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


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


  • 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


Biologic therapy

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


  • See Disease Characteristics

Endocrine therapy

  • See Disease Characteristics
  • No concurrent maintenance therapy comprising dexamethasone


  • 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


  • See Disease Characteristics


  • 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
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Please refer to this study by its identifier: NCT00045136

United States, Alabama
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-0006
United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Tennessee
Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
Nashville, Tennessee, United States, 37212
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Poniard Pharmaceuticals
Principal Investigator: Wendy Jenkins Poniard Pharmaceuticals
  More Information Identifier: NCT00045136     History of Changes
Other Study ID Numbers: CDR0000256377
Study First Received: September 6, 2002
Last Updated: April 2, 2009

Keywords provided by National Cancer Institute (NCI):
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on May 25, 2017