Brostallicin in Treating Patients With Recurrent or Refractory Multiple Myeloma

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Completed

Phase 2

Phase 1

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Treatments

Drug: brostallicin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00060203

PHAR1A02

CWRU-PHAR-1A02

PHARMACIA-196-ONC-0100-006

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy such as brostallicin use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of brostallicin in treating patients who have recurrent or refractory multiple myeloma.

Full description

OBJECTIVES:

Determine the objective tumor response rate (confirmed complete response and confirmed partial response) of brostallicin in patients with recurrent or refractory multiple myeloma.
Determine the maximum tolerated dose of this drug in these patients.
Determine the time to and duration of response, time to treatment failure, time to tumor progression, and survival in patients treated with this drug.
Determine the safety and tolerability of this drug in these patients.
Determine the pharmacokinetics of this drug in these patients.
Correlate baseline whole blood levels and activity of glutathione with clinical outcome in patients treated with this drug.

OUTLINE: This is an open-label, multicenter, dose-escalation study.

Phase I: Patients receive brostallicin IV over 10-30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of brostallicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Phase II: Additional patients are accrued and treated at the MTD of brostallicin as in phase I.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 23-52 patients will be accrued for this study.

Enrollment

3 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Confirmed diagnosis of multiple myeloma based on prior or current demonstration of the following criteria*:
- Major criteria:
  - Plasmacytoma on tissue biopsy
  - Bone marrow plasmacytosis with at least 30% plasma cells
  - Monoclonal globulin spike on serum electrophoresis exceeding 3.5 g/dL for IgG peaks or 2.0 g/dL for IgA peaks; greater than 1,000 mg/24hr of kappa or gamma light chain excretion on urine electrophoresis in the absence of amyloidosis
- Minor criteria:
  - Bone marrow plasmacytosis with 10% to 30% plasma cells
  - Monoclonal globulin spike present but less than levels in major criterion III above
  - Lytic bone lesions
  - Residual normal immunoglobulin M (IgM) no greater than 0.5 g/dL, IgA no greater than 0.1 g/dL, or IgG no greater than 0.6 g/dL NOTE: *Diagnosis of multiple myeloma requires a minimum of 1 major and 1 minor criterion (I and a together is not sufficient; must be I and b, I and c, I and d; II and b, II and c, II and d; III and a, III and c, III and d) or 3 minor criteria that must include a and b (a, b, and c; a, b, and d)
Measurable disease defined by 1 of the following values:
- Serum myeloma (M) protein (IgG or IgA) level greater than 1.0 g/dL
- Urine M protein (light chain disease) at least 300 mg/24hr
- Soft tissue plasmacytoma with bidimensional measurement at least 20 x 20 mm (10 x 10 mm if spiral CT scan is used)
Must have progressed during or within 12 months of discontinuing prior myelosuppressive chemotherapy (e.g., vincristine, doxorubicin, and dexamethasone (VAD) or melphalan) OR not responded after 2 courses of prior myelosuppressive chemotherapy
No indolent or smoldering myeloma or localized plasmacytoma
No known brain or leptomeningeal disease unless such lesions were previously irradiated, are currently not being treated with corticosteroids, and are associated with no clinical symptoms

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy

At least 12 weeks

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3 (at least 1,000/mm^3 if neutropenia due to replacement of the normal bone marrow cells by myeloma cells)
Platelet count at least 100,000/mm^3 (at least 50,000/mm^3 if thrombocytopenia due to replacement of the normal bone marrow cells by myeloma cells)
Hemoglobin at least 8.0 g/dL (no transfusion allowed)
No hyperviscosity syndrome

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
Serum glutamate oxaloacetate transaminase (SGOT) no greater than 2.5 times ULN
Alkaline phosphatase no greater than 2.5 times ULN

Renal

Creatinine no greater than 3.0 times ULN
Calcium no greater than 12 mg/dL

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and sampling for study analysis
HIV negative
No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
No AIDS-related illness
No active infectious process or other severe concurrent disease that would make the patient inappropriate for study entry
No mental incapacity or psychiatric illness that would preclude giving informed consent or completing follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Chemotherapy
No concurrent anticancer biological response modifiers
No concurrent immunotherapy
No concurrent sargramostim (GM-CSF)

Chemotherapy

See Disease Characteristics
More than 2 years since prior high-dose chemotherapy with autologous bone marrow transplantation or stem cell support
More than 4 weeks since prior myelosuppressive chemotherapy
No other concurrent anticancer chemotherapy

Endocrine therapy

See Disease Characteristics
No concurrent anticancer hormonal therapy
No concurrent chronic steroids
- Acute pulse dosing required for treatment of a concurrent medical condition is allowed, provided treatment duration is no greater than 2 weeks
No concurrent corticosteroids (e.g., dexamethasone)

Radiotherapy

More than 14 days since prior radiotherapy
No prior radiotherapy to more than 25% of bone marrow
No plans for radiotherapy within the next 6 months
Concurrent palliative radiotherapy for skeletal pain allowed

Surgery

More than 14 days since prior surgery
No plans for surgery within the next 6 months

Other

Acute toxic effects of prior therapy (except for alopecia and neurotoxicity) must have resolved to grade 0, 1, or the patient's baseline
- Treatment-related neurotoxicity must have resolved to the patient's baseline, not to exceed grade 2
Chronic bisphosphonates for bone pain allowed only for maintenance doses
More than 2 weeks since prior nonmyelosuppressive antimyeloma therapy
More than 2 weeks since prior macrolide antibiotics
No other concurrent investigational agents
No concurrent macrolide antibiotics
No concurrent participation in another treatment clinical study