Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01078441
First received: February 27, 2010
Last updated: June 3, 2013
Last verified: June 2013
  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: pegylated liposomal doxorubicin hydrochloride
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 overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan and Meier


Secondary Outcome Measures:
  • Response rates (CR+PR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Median time to progression [ Time Frame: From relapse until disease progression, up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan and Meier.

  • Toxicity event rate assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 45
Study Start Date: September 2010
Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (combination chemotherapy)
Patients receive bortezomib IV on days 1, 4, 8, and 11; pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 4; oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12; and cyclophosphamide IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • CAELYX
  • Dox-SL
  • DOXIL
  • doxorubicin hydrochloride liposome
  • LipoDox
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: dexamethasone
Given orally
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the 1-year survival of patients with relapsed multiple myeloma treated with bortezomib, pegylated liposomal doxorubicin hydrochloride, 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 IV on days 1, 4, 8, and 11; pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 4; oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12; and cyclophosphamide IV over 2 hours on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Peripheral blood and bone marrow samples may be collected for future research. Patients complete the 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
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)

    • No more than two lines of prior therapy for multiple myeloma, including the autologous SCT (autologous SCT, preceding induction therapy, and any maintenance therapy will be considered one line of therapy)
    • No therapy for relapsed disease following 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
  • Hemoglobin > 8 g/dL
  • Platelet count ≥ 75,000/mm^3 (without transfusion support)
  • ANC ≥ 1,000/mm^3 (without use of growth factors)
  • Creatinine < 2.5 mg/dL
  • Direct bilirubin ≤ 1.5 mg/dL
  • ALT and AST ≤ 2.5 times upper limit of normal
  • LVEF normal by ECHO or MUGA scan
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active, uncontrolled seizure disorder
  • No seizures within the past 6 months
  • No 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
  • No peripheral neuropathy ≥ grade 2 according to the CTEP active version of the NCI CTCAE
  • 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
  • No known allergy to bortezomib or anthracyclines
  • At least 14 days since prior palliative and/or localized radiotherapy
  • No prior allogeneic SCT
  • No prior doxorubicin hydrochloride exposure > 240 mg/m^2
  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
Investigators
Principal Investigator: Shaji Kumar Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01078441     History of Changes
Other Study ID Numbers: NCI-2011-02002, E2A08, CDR0000663822, U10CA021115
Study First Received: February 27, 2010
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Liposomal doxorubicin
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 20, 2014