Title
Chemotherapy, Holmium Ho 166 DOTMP, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma
A Multicenter Dosimetry Trial to Evaluate Radiation Absorbed Dose From Holmium-166-DOTMP in Patients With Multiple Myeloma
Phase
Phase 1/Phase 2Lead Sponsor
Poniard PharmaceuticalsStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Multiple Myeloma and Plasma Cell NeoplasmIntervention/Treatment
ho166-dotmp melphalan autologous hematopoietic stem cells ...Study Participants
NoneRATIONALE: 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.
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.
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
