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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045136
First received: September 6, 2002
Last updated: April 2, 2009
Last verified: April 2009
  Purpose

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:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045136

Locations
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
Investigators
Principal Investigator: Wendy Jenkins Poniard Pharmaceuticals
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00045136     History of Changes
Other Study ID Numbers: CDR0000256377, PONIARD-0102, NEORX-0102, FHCRC-1704.00
Study First Received: September 6, 2002
Last Updated: April 2, 2009
Health Authority: United States: Federal Government

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:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014