NCT00083564

Brief Summary

STR (Skeletal Targeted Radiotherapy, 166Ho-DOTMP) is an investigational radiopharmaceutical that delivers radiation directly to cancer cells in the bone and bone marrow. Conventional methods of delivering radiation therapy, such as total body irradiation, expose non-target tissues to radiation and cause serious side effects. In contrast, STR's targeted approach to delivering radiotherapy concentrates the radiation where it is needed, and minimizes exposure of normal tissues. STR is composed of a bone-targeting molecule, DOTMP, in a stable complex with the radionuclide holmium-166. When injected into a patient's bloodstream, STR rapidly binds to bone mineral, delivering a brief, intense dose of radiation to destroy cancer cells in the bone and marrow. The high-energy and long path-length of holmium-166 beta particles provide optimal penetration and uniform irradiation of disease sites in the marrow and bone. STR that does not bind to bone is rapidly eliminated through the urinary tract. STR treatment is followed by autologous stem cell transplantation. The short half-life of holmium-166 allows treatment on an out-patient basis, and minimizes the time required between STR administration and transplantation. The phase III study of STR is a multi-center, randomized, controlled study, designed to evaluate the safety and efficacy of STR in patients with primary refractory multiple myeloma. These are patients who have failed to achieve at least a partial response to conventional therapy and have been undergoing treatment for less than 18 months. The trial is expected to enroll approximately 240 evaluable patients, half on the experimental arm and half on the control arm. Patients on the experimental arm will receive STR at a dose of 750 mCi/m2 plus the chemotherapy drug melphalan at 200 mg/m2, followed by autologous stem cell transplantation. Patients on the control arm will receive melphalan only, followed by transplantation. Patients on both study arms will be evaluated for response to treatment six months after transplantation, using an immunofixation assay to detect myeloma protein in patient samples. Analysis of patient samples will be conducted at a central laboratory, and blinded results will be reviewed by an independent panel of experts. The study's primary endpoint is complete response, as determined by the complete disappearance of myeloma protein at six months post-transplant.

Trial Health

40
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P25-P50 for phase_3 multiple-myeloma

Geographic Reach
2 countries

21 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2004

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

May 25, 2004

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 28, 2004

Completed
Last Updated

March 31, 2009

Status Verified

March 1, 2009

First QC Date

May 25, 2004

Last Update Submit

March 30, 2009

Conditions

Multiple Myeloma

Keywords

Multiple myelomaPrimary refractory multiple myelomaSTRSkeletal Targeted RadiotherapyHolmium-166166-Ho-DOTMP

Interventions

STR(TM) (Skeletal Targeted Radiotherapy, Holmium-166-DOTMP)DRUG

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • A subject must meet all of the following criteria to be eligible for the study. These will be evaluated within four weeks prior to enrollment.
  • Subject must have primary refractory multiple myeloma defined as having failed to achieve an objective response (CR or PR using EBMT/IBMTR/ABMTR criteria) to any therapy since the initiation of induction therapy. At least one previous therapy must be a qualifying therapy that includes high dose pulsed steroids.
  • There must be \< 18 months from the beginning of induction therapy to time of enrollment on study.
  • Subject must meet institutional guidelines for autologous PBSCT.
  • Subject must have a minimum of 2 x 106 unmanipulated CD34+ cells/kg cryopreserved and available for transplant.
  • Age 18 and 70 years.
  • Adequate pulmonary function defined by FEV1, FVC and DLCO \> or = 50% of predicted.
  • Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of \> or = 45%, with no evidence of cardiac amyloidosis.
  • Adequate liver function, defined as serum total bilirubin \< or = 2x institutional laboratory upper limit of normal and ALT/SGPT \< or = 3x institutional laboratory upper limit of normal.
  • Adequate renal function, defined as 24 hour measured creatinine clearance of \> or = 50 mL/min/1.73 m2 BSA and serum creatinine \< or = 1.8 mg/dL.
  • ECOG performance score (PS) of 0, 1, or 2.
  • Women of childbearing potential must have a negative pregnancy test (serum or urine beta HCG) and be using appropriate birth control methods.
  • Ability to understand the study and provide informed consent.

You may not qualify if:

  • A subject meeting any of the following criteria is not eligible for participation in the study:
  • Non-secretory multiple myeloma.
  • Asymptomatic MGUS, smoldering multiple myeloma, or indolent multiple myeloma.
  • Solitary bone or extramedullary plasmacytoma.
  • Waldenstrom's macroglobulinemia (IgM myeloma).
  • Evidence of disease progression (such as new bone lesions) in the setting of a greater than 50% reduction in M-protein.
  • Absence of previous therapy with pulsed corticosteroids for multiple myeloma.
  • Previous high-dose therapy with stem cell or bone marrow transplant, including autologous, allogeneic, and reduced-intensity or non-myeloablative allogeneic transplants.
  • Life expectancy severely limited by concomitant illness (less than 6 months).
  • Evidence of symptomatic spinal cord compression or pathological fracture within 3 months.
  • Cumulative external beam radiation to \> 20% of marrow volume or \> 40 Gy to any single region of the spinal cord.
  • Prior radiation to the bladder or kidney, defined as radiation portals that directly include any volume of either kidney or the bladder.
  • Uncontrolled arrhythmia or symptomatic cardiac disease.
  • Clinical evidence of amyloidosis involving the heart, lungs, liver, kidney, autonomic nervous system, or GI tract.
  • History of hemorrhagic cystitis.
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

University of Alabama

Birmingham, Alabama, 35249, United States

Location

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Wayne State University, Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53208, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

  • Giralt S, Bensinger W, Goodman M, Podoloff D, Eary J, Wendt R, Alexanian R, Weber D, Maloney D, Holmberg L, Rajandran J, Breitz H, Ghalie R, Champlin R. 166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials. Blood. 2003 Oct 1;102(7):2684-91. doi: 10.1182/blood-2002-10-3250. Epub 2003 May 1.

    PMID: 12730103BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

holmium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetrakis(methylenephosphonic acid)

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

May 25, 2004

First Posted

May 28, 2004

Study Start

March 1, 2004

Last Updated

March 31, 2009

Record last verified: 2009-03

Locations

US(20)CA(1)