Neoplasms

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Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

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Melphalan

Lenograstim

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

filgrastim

melphalan

peripheral blood stem cell transplantation

holmium Ho 166 DOTMP

William I. Bensinger, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radioactive drugs such as holmium Ho 166 DOTMP can kill cancer cells without harming healthy cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of melphalan with or without holmium Ho 166 DOTMP followed by peripheral stem cell transplantation in treating patients who have multiple myeloma.

OBJECTIVES: I. Compare the efficacy of melphalan with or without holmium Ho 166 DOTMP followed by autologous peripheral blood stem cell transplantation in patients with multiple myeloma. II. Compare the response rate and overall survival of these patients treated with these regimens. III. Compare the hematologic recovery rate and time to granulocyte engraftment of these patients treated with these regimens. IV. Compare the toxicity of these regimens in this patient population.

OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to their beta 2 microglobulin (B2M) test at initial diagnosis (B2M no greater than 4 mg/L vs B2M greater than 4 mg/L vs unknown B2M). Patients are randomized to one of two treatment arms. Prior to stratification and randomization, patients receive a diagnostic dose of holmium Ho 166 DOTMP within days -31 to -10. Patients with adequate skeletal uptake of the diagnostic dose are randomized for therapy. Arm I: Patients receive holmium Ho 166 DOTMP IV over no more than 10 minutes within days -10 to -7 (at least 1 week and no more than 3 weeks after the diagnostic dose), melphalan IV over 20-30 minutes within days -3 to -1 (at least 24 hours prior to autologous peripheral blood stem cell (PBSC) transplantation), and autologous PBSC transplantation on day 0. Arm II: Patients receive melphalan and autologous PBSC transplantation as in arm I. Following transplantation, patients receive filgrastim (G-CSF) daily until blood counts recover. Patients are followed at 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 300 patients (150 per treatment arm) will be accrued for this study within 9 months.

Melphalan With or Without Holmium Ho 166 DOTMP Followed by Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

A Phase III Multicenter, Randomized, Open-Label Trial Evaluating High Dose Melphalan Plus Holmium-166-DOTMP Versus High Dose Melphalan Alone When Given In Conjuction With Peripheral Blood Stem Cell Transplantation In Patients With Multiple Myeloma

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Wendy Jenkins

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.

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.

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

Poniard Pharmaceuticals

RATIONALE: Radiation therapy using holmium Ho 166 DOTMP may damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy using holmium Ho 166 DOTMP plus melphalan and peripheral stem cell transplantation in treating patients who have multiple myeloma.

OBJECTIVES: I. Determine the maximum tolerated dose of targeted radiotherapy using holmium Ho 166 DOTMP when combined with melphalan and autologous or syngeneic peripheral blood stem cell transplantation in patients with multiple myeloma. II. Determine the response rate and time to progression in patients treated with this regimen.

OUTLINE: This is a dose escalation, multicenter study of targeted radiotherapy using holmium Ho 166 DOTMP. Phase I: Autologous or syngeneic peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells. Patients receive an initial test dose of holmium Ho 166 DOTMP IV. Patients with adequate skeletal uptake of the test dose then receive therapeutic dose holmium Ho 166 DOTMP IV over 5-10 minutes for 1-3 days beginning 2 days after test dose infusion and melphalan IV over 20-30 minutes on day -3. PBSC are reinfused beginning a minimum of 24 hours after melphalan infusion and after ongoing radiation to bone marrow falls to less than 1 rad/hour. Cohorts of 4-7 patients receive escalating doses of targeted radiotherapy using holmium Ho 166 DOTMP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 7 patients experience dose limiting toxicity. Phase II: Patients receive holmium Ho 166 DOTMP at the MTD from phase I of the study. Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 1 year.

Radiation Therapy Using Holmium Ho 166 DOTMP Plus Melphalan and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

A Phase I/II Study of Targeted Radiotherapy Using Holmium-166-DOTMP With Melphalan and Peripheral Blood Stem Cell Transplantation for Treatment of Multiple Myeloma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Melphalan With or Without Holmium Ho 166 DOTMP Followed by Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma	NCT00008229	Multiple Myelom...	filgrastim melphalan peripheral bloo... holmium Ho 166 ...	18 Years - 70 Years	Fred Hutchinson Cancer Center
Chemotherapy, Holmium Ho 166 DOTMP, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma	NCT00045136	Multiple Myelom...	melphalan peripheral bloo... holmium Ho 166 ...	18 Years - 70 Years	National Cancer Institute (NCI)
Melphalan With or Without Holmium Ho 166 DOTMP Followed by Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma	NCT00008229	Multiple Myelom...	filgrastim melphalan peripheral bloo... holmium Ho 166 ...	18 Years - 70 Years	Fred Hutchinson Cancer Center
Radiation Therapy Using Holmium Ho 166 DOTMP Plus Melphalan and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma	NCT00004158	Multiple Myelom...	melphalan peripheral bloo... holmium Ho 166 ...	18 Years - 65 Years	Fred Hutchinson Cancer Center
Radiation Therapy Using Holmium Ho 166 DOTMP Plus Melphalan and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma	NCT00004158	Multiple Myelom...	melphalan peripheral bloo... holmium Ho 166 ...	18 Years - 65 Years	Fred Hutchinson Cancer Center
Chemotherapy, Holmium Ho 166 DOTMP, and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma	NCT00045136	Multiple Myelom...	melphalan peripheral bloo... holmium Ho 166 ...	18 Years - 70 Years	National Cancer Institute (NCI)

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