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A Phase I Study of Samarium Sm-153 Lexidronam Combined With Bortezomib for Patients With Relapsed or Refractory Multiple Myeloma


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

A Phase I Study of Samarium Sm-153 Lexidronam Combined With Bortezomib for Patients With Relapsed or Refractory Multiple Myeloma


OBJECTIVES:

Primary

- Assess the safety and tolerability (maximum tolerated dose and dose-limiting toxicity)
of samarium Sm 153 lexidronam pentasodium and bortezomib in patients with relapsed or
refractory multiple myeloma.

Secondary

- Determine the response rate (combined complete response, partial response, and minimal
response) in patients treated with this regimen.

- Determine the time to response and the time to progression of disease in patients
treated with this regimen.

- Determine the progression-free survival and overall survival of patients treated with
this regimen.

- Assess the antitumor effects of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of samarium Sm 153 lexidronam
pentasodium.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and samarium Sm 153
lexidronam pentasodium IV on day 3. Treatment repeats every 8 weeks for up to 4 courses in
the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of samarium Sm 153 lexidronam pentasodium
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 6 patients experience dose-limiting toxicity. The MTD of
samarium Sm 153 lexidronam pentasodium is determined with 2 different doses of bortezomib.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosed with multiple myeloma by 1 of the following criteria:

- Meets any 2 of the following major criteria:

- Plasmacytomas on tissue biopsy

- Bone marrow plasmacytosis (i.e., > 30% plasma cells)

- Monoclonal immunoglobulin spike IgG > 3.5 g/dL or IgA > 2.0 g/dL by serum
electrophoresis; kappa or lambda light chain excretion > 1 g by 24-hour
urine protein electrophoresis

- Plasmacytomas on tissue biopsy AND meets any 1 of the following minor criteria:

- Presence of monoclonal immunoglobulin at a lesser magnitude than given
under above major criteria

- Lytic bone lesions

- Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

- Monoclonal immunoglobulin spike IgG > 3.5 g/dL or IgA > 2.0 g/dL by serum
electrophoresis; kappa or lambda light chain excretion > 1 g by 24-hour urine
protein electrophoresis AND meets 1 of the following minor criteria:

- Bone marrow plasmacytosis (i.e., 10-30% plasma cells)

- Lytic bone lesions

- Presence of monoclonal immunoglobulin at a lesser magnitude than given under
major criteria with bone marrow plasmacytosis (i.e., 10-30% plasma cells) AND
meets 1 of the following minor criteria:

- Lytic bone lesions

- Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

- Measurable disease, defined as a monoclonal immunoglobulin spike of ≥ 1 gm/dL by
serum electrophoresis and/or a immunoglobulin spike of ≥ 200 mg by 24-hour urine
protein electrophoresis or evidence of lytic bone disease OR

- Nonmeasurable disease (i.e., patients with nonsecretory or oligosecretory multiple
myeloma)

- Relapsed or refractory disease

- Relapsed disease following a response or stable disease after prior chemotherapy
(e.g., single-agent steroids, vincristine, doxorubicin, and dexamethasone [VAD],
or melphalan and prednisone [MP]) or high-dose chemotherapy

- Refractory (i.e., failure to achieve at least complete or partial response or
stable disease) to the most recent chemotherapy with or without systemic
corticosteroids

- No plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy,
monoclonal protein (M-protein), and skin changes (POEMS syndrome)

- No extramedullary myeloma

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Life expectancy > 3 months

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 75,000/mm³

- AST and ALT ≤ 3 times upper limit of normal (ULN)

- Bilirubin ≤ 2 times ULN (unless clearly related to disease)

- Creatinine clearance ≥ 30 mL/min

- Creatinine clearance > 15 mL/min and < 30 mL/min due to significant myelomatous
involvement of kidneys allowed at discretion of investigator

- Sodium > 130 mmol/L

- No ECG evidence of acute ischemia or new conduction system abnormalities

- No myocardial infarction within the past 6 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active infection

- No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL)

- No New York Hospital Association class III or IV heart failure

- No poorly controlled hypertension, diabetes mellitus, or other serious medical or
psychiatric illness that would preclude study treatment

- No known HIV history

- No known active hepatitis B or C viral infection

- No history of allergic reaction attributable to compounds of similar chemical or
biological composition to bortezomib, boron, mannitol,
ethylenediaminetetramethylenephosphonic acid (EDTMP), or phosphonates

- No peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

- At least 12 weeks since prior samarium Sm 153 lexidronam pentasodium

- No more than 1 prior treatment

- At least 24 weeks since prior strontium chloride Sr 89

- No more than 1 prior treatment

- No major surgery within the past 4 weeks

- No chemotherapy within the past 3 weeks (6 weeks for nitrosoureas)

- No corticosteroids (> 10 mg/day prednisone or equivalent) within the past 3 weeks

- No immunotherapy, antibody therapy, or radiotherapy (except localized radiotherapy)
within the past 4 weeks

- No other concurrent investigational agents

- No concurrent corticosteroids (≥ 10 mg prednisone or equivalent)

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose and dose-limiting toxicity

Safety Issue:

Yes

Principal Investigator

James R. Berenson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Oncotherapeutics

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000479712

NCT ID:

NCT00316940

Start Date:

December 2005

Completion Date:

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • refractory multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma

Name

Location

Comprehensive Blood and Cancer CenterBakersfield, California  93309
Fountain Valley, California  92708
Hematology-Oncology Medical Group of Fresno, IncorporatedFresno, California  93720
Center for Cancer and Blood Disorders at Suburban HospitalBethesda, Maryland  20817