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

Sponsor

Poniard Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00045136

Collaborator

(none)

Locations

Study Details

Study Description

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.

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

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Multicenter Dosimetry Trial to Evaluate Radiation Absorbed Dose From Holmium-166-DOTMP in Patients With Multiple Myeloma

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Jan 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-0006
2	University of California Davis Cancer Center	Sacramento	California	United States	95817
3	Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus	Nashville	Tennessee	United States	37212
4	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
5	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024