Know Cancer

or
forgot password

Phase I/II Study of Liposomal Doxorubicin (Doxil®)/ Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Multiple Myeloma and Plasma Cell Neoplasm

Thank you

Trial Information

Phase I/II Study of Liposomal Doxorubicin (Doxil®)/ Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma


OBJECTIVES:

Primary

- Determine the safety and tolerability of doxorubicin HCl liposome, melphalan, and
bortezomib in patients with relapsed or refractory stage I-III multiple myeloma.

- Determine the maximum tolerated dose (MTD) of this regimen in these patients.

Secondary

- Determine the overall response rate, including complete, near-complete, partial, and
minimal response rate, in patients treated with this regimen.

- Determine the time to response, progression-free survival, and overall survival of
patients treated with this regimen.

- Determine the toxic effects of this regimen at the MTD in these patients.

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study.

- Phase I: Patients receive doxorubicin HCl liposome IV over 30-60 minutes and melphalan
IV over 30 minutes on day 1 and bortezomib IV on days 1, 4, 8, and 11. Treatment
repeats every 28 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, melphalan, and
bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 3 or 4 of 6 patients experience dose-limiting toxicity
after 2 courses of therapy.

- Phase II: Patients receive doxorubicin HCl liposome, melphalan, and bortezomib at the
MTD as in phase I.

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

PROJECTED ACCRUAL: Approximately 32 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of multiple myeloma

- Stage I, II, or III disease according to Durie-Salmon staging criteria

- Progressive disease, defined as one of the following:

- For secretory disease:

- A 25% increase in serum M-protein or Bence Jones protein (an absolute
increase of 0.5 g/dL serum M-protein or ≥ 200 mg/24 hours of urine light
chain excretion)

- For nonsecretory disease:

- Bone marrow biopsy with > 25% increase in plasma cells or an absolute
increase of ≥ 10% over prior known level

- Development of new or worsening existing lytic bone lesions or soft tissue
plasmacytomas

- Hypercalcemia (i.e., calcium > 11.5 mg/dL)

- Relapsed after complete response

- Must have received ≥ 2 of the following therapeutic regimens for multiple myeloma:

- Nonmyeloablative transplantation

- No significant graft-versus-host disease

- At least 30 days since prior immunosuppressive therapy (concurrent
prednisone allowed provided dose is ≤ 10 mg daily)

- Mobilization with chemotherapy followed by either single or tandem autologous
stem cell transplantation (considered 1 prior regimen)

- Mobilization with chemotherapy followed by autologous and subsequent
nonmyeloablative allogeneic stem cell transplantation (considered 1 prior
regimen)

- Any combination of drugs given concurrently (considered 1 prior regimen)

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- Absolute neutrophil count > 1,000/mm^3 (no colony-stimulating factors)

- Platelet count > 50,000/mm^3 (no transfusion support)

- Bilirubin ≤ 2.0 mg/dL

- AST ≤ 4 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 weeks after
completion of study treatment

- No history of allergic reaction to compounds containing boron or mannitol

- No active uncontrolled viral (including HIV), bacterial, or fungal infection

- No motor or sensory neuropathy ≥ grade 2

- No myocardial infarction within the past 6 months

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

- No uncontrolled angina

- No severe uncontrolled arrhythmia

- No acute ischemia by EKG

- LVEF ≥ 35% by MUGA (MUGA required in patients whose lifetime cumulative doxorubicin
hydrochloride dose > 400 mg/m^2)

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No grade III or IV toxicity due to previous antineoplastic therapy (except alopecia)

- At least 3 weeks since prior chemotherapy

- No prior doxorubicin HCl liposome, melphalan, and bortezomib as combination therapy
(single or two-drug combinations of these are allowed)

- No concurrent corticosteroids (≤ 10 mg prednisone/day or equivalent allowed)

- No other concurrent chemotherapy

- No concurrent thalidomide

- No other concurrent investigational therapy

- No other concurrent antineoplastic treatment for multiple myeloma, including
clarithromycin

- No concurrent radiation therapy

- No concurrent nonsteroidal anti-inflammatory agents

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Proportion of patients experiencing treatment-related ≥ grade 3 hematologic or nonhematologic toxicity or treatment-related death (phase I)

Safety Issue:

Yes

Principal Investigator

Ajai Chari, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Herbert Irving Comprehensive Cancer Center

Authority:

Unspecified

Study ID:

CDR0000471769

NCT ID:

NCT00334932

Start Date:

February 2006

Completion Date:

Related Keywords:

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

Name

Location

UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032