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Phase II Study of Bortezomib (PS-341) and Pegylated Liposomal Doxorubicin as Initial Therapy for Adult Patients With Symptomatic Multiple Myeloma

Phase 2
18 Years
Open (Enrolling)
Extramedullary Plasmacytoma, Isolated Plasmacytoma of Bone, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

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Trial Information

Phase II Study of Bortezomib (PS-341) and Pegylated Liposomal Doxorubicin as Initial Therapy for Adult Patients With Symptomatic Multiple Myeloma


I. To evaluate the complete response (CR) + near-complete response (nCR) rate of the
bortezomib /pegylated liposomal doxorubicin regimen in patients with previously untreated,
symptomatic multiple myeloma.

II. To evaluate the toxicity of the bortezomib/pegylated liposomal doxorubicin regimen in
patients with previously untreated, symptomatic multiple myeloma.


I. To evaluate the overall response rate, including patients with CR, nCR, and partial
response (PR), of the bortezomib/pegylated liposomal doxorubicin regimen in patients with
previously untreated, symptomatic multiple myeloma. Data for minor responses (MR) and stable
disease (SD), as well as progressive disease (PD) will be collected as well.

II. To evaluate the impact of therapy with the bortezomib/pegylated liposomal doxorubicin
regimen on the ability to collect peripheral blood stem cells in those patients going on to
subsequent autologous stem cell transplantation. Data will also be collected about the
engraftment characteristics of those patients who undergo transplantation, including the
number of days to achieve an ANC of 500, a platelet count of 100,000, and packed red blood
cell and platelet transfusion independence.

III. To evaluate the time to progression (TTP) in all patients receiving
bortezomib/pegylated liposomal doxorubicin therapy, both those who go on to autologous stem
cell transplantation and those who do not go on to transplantation.

IV. To evaluate the value of early changes in levels of serum interleukin 6 (IL-6) and
macrophage inflammatory protein 1 alpha (MIP-1α) as predictors of response to
bortezomib/pegylated liposomal doxorubicin.

V. To correlate pre-treatment clinical and biological characteristics with response to
therapy and toxicity.


Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and pegylated
doxorubicin HCl liposome IV over 1 hour on day 4. Treatment repeats every 21 days for up to
8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 weeks for 2 years and then every 6 months for up to 5 years.

Inclusion Criteria:

- Patients must have a histologically confirmed diagnosis of symptomatic multiple
myeloma with evaluable disease parameters

- Patients may not have undergone any prior therapy, with the following exceptions:

- Prior plasmapheresis with plasma exchange (PLEX) for a hyperviscosity syndrome
is allowed, providing the patient has no current evidence of hyperviscosity and
has not required PLEX for at least one week prior to initiation of therapy

- Prior radiation therapy to areas of spinal cord compression by plasmacytomas,
painful lesions due to bony involvement, or other myeloma related indications,
is allowed provided that radiation will have been completed 3 weeks before
initiation of therapy

- Prior surgical intervention, such as for bony fractures or other myeloma related
complications, is allowed provided that this will have been completed 3 weeks
before the initiation of therapy, and patients have recovered from surgery

- Prior therapy with corticosteroids for indications other than multiple myeloma
is allowed, provided such therapy has been discontinued at least two weeks prior
to study entry, and at least two weeks before their baseline disease evaluation

- Prior supportive therapy with bisphosphonates or erythropoietin is allowed

- Non-pregnant and Non-nursing

- Inclusion of females of childbearing potential requires a negative pregnancy

- ECOG Performance Status =< 2

- Patients may not have a prior history of a hypersensitivity reaction to pegylated
liposomal doxorubicin or doxorubicin, bortezomib or other boronic acid-based
compounds; patients with a history of reactions to liposomal drug formulations other
than Pegylated liposomal doxorubicin will be evaluated individually, and if their
reactions were felt to have been due to the liposomal component itself, as opposed to
the encapsulated agent, they will be excluded at the discretion of the investigators

- Patients who are known to be HIV-seropositive and are taking anti-retrovirals may not
participate in this study because of potential interactions between these medications
and the investigational agent; patients who are HIV seropositive and not on
anti-retroviral therapy, and who otherwise meet the organ function criteria, will be
eligible for the study

- Patients who are known to have active hepatitis A, B, or C viral infection may not
participate in this study; active disease is defined as patients with a known viral
hepatitis whose liver function tests are elevated beyond the criteria indicated

- No EKG evidence of acute ischemia

- No EKG evidence of medically significant conduction system abnormalities

- No history of myocardial infarction within the last 6 months

- Left ventricular ejection fraction (LVEF) must be >= 45% by either echocardiography
or radionuclide-based multiple gated acquisition (RNV or MUGA)

- No Class 3 or Class 4 New York Heart Association Congestive Heart Failure

- Creatinine < 2.5 mg/dL

- ALT (SGPT) and AST (SGOT) =< 2.5 times the upper limit of the institutional normal

- Total bilirubin =< 1.2 times the upper limit of the institutional normal value

- ANC >= 1,000/ul

- Platelets >= 100,000/ul

- Hemoglobin >= 8 g/dl (transfusion- and/or growth factor-dependent patients are not
excluded if the above parameters can be achieved with such support)

- For those patients receiving warfarin (Coumadin), unfractionated Heparin, or
low-molecular weight Heparin therapy, the applicable coagulation parameter that is
being monitored must be within the accepted therapeutic ranges for those indications

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete plus near-complete (CR + nCR) response rate

Outcome Description:

Evaluated using the criteria of Blade et al. with the additional category or near-CR as defined by Richardson et al. Estimated with an exact 90% confidence interval.

Outcome Time Frame:

126 days

Safety Issue:


Principal Investigator

Robert Orlowski

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B


United States: Food and Drug Administration

Study ID:




Start Date:

June 2004

Completion Date:

Related Keywords:

  • Extramedullary Plasmacytoma
  • Isolated Plasmacytoma of Bone
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



University of North CarolinaChapel Hill, North Carolina  27599
Cancer and Leukemia Group BChicago, Illinois  60606