Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant

Phase 2

Terminated

Conditions: Refractory Multiple Myeloma

Interventions: Drug: liposomal doxorubicin
Drug: bortezomib
Drug: dexamethasone
Drug: cyclophosphamide

Registration Number: NCT01078441

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is studying how well giving bortezomib together with liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide works in treating patients with multiple myeloma that relapsed after autologous stem cell transplant. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide may kill more cancer cells.

Detailed Description: PRIMARY OBJECTIVES:

I. To evaluate the 1-year survival of patients with relapsed multiple myeloma treated with bortezomib, liposomal doxorubicin, dexamethasone, and cyclophosphamide.

SECONDARY OBJECTIVES:

I. To evaluate response rates in patients treated with this regimen.

II. To evaluate the median time to progression in patients treated with this regimen.

III. To evaluate the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Peripheral blood and bone marrow samples may be collected for future research. Patients complete the Functional Assessment of Cancer Therapy (FACT) neurotoxicity questionnaire periodically.

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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

Inclusion Criteria

Diagnosis of multiple myeloma that was symptomatic at the time of initial diagnosis
Must have met the following criteria at one point during the disease course:
- Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy-proven plasmacytoma
- Symptomatic disease at initial diagnosis that prompted the initiation of therapy as well as evidence of end-organ damage at the time of diagnosis, including at least 1 of the following:
  - Anemia
  - Hypercalcemia
  - Bone disease (lytic bone lesions or pathologic fracture)
  - Renal dysfunction
Disease relapsed < 12 months after autologous stem cell transplantation (SCT)
Measurable disease, as defined by the presence of ≥ 1 of the following:
- Serum M-spike ≥ 1 g/dL
- Urine M-spike ≥ 200 mg/24 hours
- Involved free light chain (FLC) ≥ 10 mg/dL (provided the serum FLC is abnormal)
- Plasma cells ≥ 30%
ECOG performance status 0-2
Negative pregnancy test
Fertile patients must use effective contraception
At least 14 days since prior palliative and/or localized radiotherapy
Left ventricular ejection fraction (LVEF) normal by Echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan
Hemoglobin > 8 g/dL
Platelet count ≥ 75,000/mm^3 (without transfusion support)
Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (without use of growth factors)
Creatinine < 2.5 mg/dL
Direct bilirubin ≤ 1.5 mg/dL
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal
All tests below must be performed within 14 days prior to registration:
- Serum free light chain assay
- Kappa free light chain
- Lambda free light chain
Prior malignancy allowed provided it was treated curatively and has not relapsed in 5 years
- Patients with basal cell skin cancer, in situ cervical cancer, or prostate cancer not requiring therapy are eligible

Exclusion Criteria

Therapy for relapsed disease following SCT
Known allergy to bortezomib or anthracyclines
Prior allogeneic SCT
Peripheral neuropathy ≥ grade 2 according to the Cancer Therapy Evaluation Program (CTEP) active version of the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Concurrent uncontrolled illness that would limit study compliance, including the following:
- Uncontrolled hypertension
- Symptomatic congestive heart failure
- Unstable angina
- Uncontrolled cardiac arrhythmia
- Uncontrolled psychiatric illness or social situation
- Active uncontrolled infection
Prior doxorubicin hydrochloride exposure > 240 mg/m^2
Active, uncontrolled seizure disorder
Seizures within the past 6 months
Pregnant or nursing

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (combination chemotherapy)	liposomal doxorubicin	Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Treatment (combination chemotherapy)	bortezomib	Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Treatment (combination chemotherapy)	cyclophosphamide	Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Treatment (combination chemotherapy)	dexamethasone	Patients receive bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, and 15; liposomal doxorubicin 30 mg/m2 intravenously (IV) over 1 hour on day 4; oral dexamethasone 20mg on days 1, 2, 8, 9, 15 and 16; and cyclophosphamide 750 mg/m2 IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
One-year Survival in Patients Treated With This Regimen.	Assessed at 1 year	Proportion of patients who are still alive at 1 year after registration.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (130): Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
The Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Exempla Saint Joseph Hospital
🇺🇸
Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸
Denver, Colorado, United States
Rose Medical Center
🇺🇸
Denver, Colorado, United States
Colorado Cancer Research Program CCOP
🇺🇸
Denver, Colorado, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
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Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States