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

This study has been terminated.
(The study was closed early due to weak accrual on June 26, 2012.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01078441
First received: February 27, 2010
Last updated: January 5, 2015
Last verified: July 2014
  Purpose
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.

Condition Intervention Phase
Refractory Multiple Myeloma
Drug: liposomal doxorubicin
Drug: bortezomib
Drug: dexamethasone
Drug: cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Bortezomib, Liposomal Doxorubicin, Dexamethasone, and Cyclophosphamide in Patients With Multiple Myeloma Relapsing Within 12 Months of Autologous Stem Cell Transplant

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • One-year Survival in Patients Treated With This Regimen. [ Time Frame: Assessed at 1 year ] [ Designated as safety issue: No ]
    Proportion of patients who are still alive at 1 year after registration.


Enrollment: 2
Study Start Date: September 2010
Study Completion Date: March 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (combination chemotherapy)
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.
Drug: liposomal doxorubicin
Given IV
Other Names:
  • Doxil
  • Doxorubicin HCl Liposomal
  • Doxorubicin Hydrochloride Liposomal
  • Doxorubicin Hydrochloride Liposome
Drug: bortezomib
Given subcutaneously.
Other Names:
  • Velcade
  • PS-341
  • MLN-341
  • LDP-341
Drug: dexamethasone
Given orally
Other Names:
  • Decadron
  • Hexadrol
  • Dexameth
  • Dexone
  • DXM
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • Neosar

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01078441

  Show 130 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Study Chair: Shaji Kumar, M.D. Mayo Clinic
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01078441     History of Changes
Other Study ID Numbers: NCI-2011-02002  NCI-2011-02002  E2A08  U10CA021115 
Study First Received: February 27, 2010
Results First Received: January 5, 2015
Last Updated: January 5, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
Bortezomib
Liposomal Doxorubicin
Dexamethasone
Cyclophosphamide
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Liposomal doxorubicin
Cyclophosphamide
Doxorubicin
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on August 25, 2016