Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00609167
First received: January 31, 2008
Last updated: May 13, 2011
Last verified: May 2011

January 31, 2008
May 13, 2011
December 2006
January 2009   (final data collection date for primary outcome measure)
Number of Participants Who Achieved a Confirmed Responses Defined as a Complete Response (CR), Near CR or Very Good Partial Response (VGPR) After the First 4 Months of Treatment [ Time Frame: After 4 months of treatment ] [ Designated as safety issue: No ]

Response that was confirmed on 2 consecutive evaluations during the first 4 months of treatment.

Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.

near Complete Response (nCR): Patients who meet all criteria for CR except a positive immunofixation will be classified as nCR.

Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100mg per 24hours; <=5% plasma cells in bone marrow.

  • Proportion of confirmed responses defined as a complete response (CR), nCR, partial response (PR), or very good PR after the first 4 months of treatment [ Designated as safety issue: No ]
  • Hematological response rate [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00609167 on ClinicalTrials.gov Archive Site
  • Progression Free Survival (PFS) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

    PFS was defined as the time from registration to progression or death due to any cause.

    Progression was defined as any one or more of the following:

    An increase of 25% from lowest confirmed response in:

    • Serum M-component (absolute increase >= 0.5g/dl)
    • Urine M-component (absolute increase >= 200mg/24hour
    • Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl)
    • Bone marrow plasma cell percentage (absolute increase of >=10%)
    • Definite development of new bone lesion or soft tissue plasmacytomas
  • Overall Survival (OS) [ Time Frame: From date of registration until death (up to 5 years) ] [ Designated as safety issue: No ]
    OS was defined as the time from registration to death of any cause.
  • Number of Participants Who Responded to Treatment (Complete Response,CR; Near Complete Response, nCR; Very Good Partial Response, VGPR; or Partial Response, PR) After 4 Cycles [ Time Frame: 4 cycles ] [ Designated as safety issue: No ]

    Response that was confirmed on 2 consecutive evaluations after 8 months of treatment.

    CR, nCR and VGPR as defined in the primary outcome.

    Partial Response(PR): >=50% reduction in serum M-component and/or

    Urine M-Component >=90% reduction or <200mg per 24hours; or >=50% decrease in difference between involved and uninvolved FLC levels.

  • Duration of Response [ Time Frame: Duration of study (up to 12 cycles) ] [ Designated as safety issue: No ]
    Duration of response was calculated from the documentation (date) of first response (CR, nCR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded.
  • Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 8 Cycles [ Time Frame: After 8 cycles of treatment ] [ Designated as safety issue: No ]

    Response that was confirmed on 2 consecutive evaluations after 8 cycles of treatment.

    Criteria for CR, nCR, VGPR and PR are defined in prior outcomes.

  • Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 12 Cycles [ Time Frame: After 12 cycles of treatment ] [ Designated as safety issue: No ]

    Response that was confirmed on 2 consecutive evaluations after 12 cycles of treatment.

    Criteria for CR, nCR, VGPR and PR are defined in prior outcomes.

  • Number of Participants With Severe Adverse Events [ Time Frame: Every cycle during treatment (up to 12 cycles) ] [ Designated as safety issue: Yes ]
    Severe adverse events were defined as grade 3 or higher, regardless of attribution to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
  • Participants Who Successfully Completed Collection of Peripheral Blood Stem Cells for Transplant [ Time Frame: After 4 cycles of treatment ] [ Designated as safety issue: No ]
    Evaluation of the ability to successfully collect peripheral blood stem cells following four months (cycles) of combination therapy.
  • Progression-free survival [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Stem cell collection and engraftment [ Designated as safety issue: No ]
  • Ability to induce complete response rate beyond 4 courses at completion of planned therapy [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
A Phase II Trial of Cyclophosphamide, Bortezomib and Dexamethasone (CYBOR-D) in Patients With Newly Diagnosed Active Multiple Myeloma

RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and dexamethasone work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide and dexamethasone together with bortezomib may kill more cancer cells.

PURPOSE: This phase II trial is studying giving cyclophosphamide and dexamethasone together with bortezomib to see how well it works in treating patients with newly diagnosed multiple myeloma.

OBJECTIVES:

Primary

* To evaluate the response rate (complete response [CR], near CR [nCR], and very good partial response) in patients with newly diagnosed multiple myeloma treated with bortezomib in combination with cyclophosphamide and dexamethasone .

Secondary

  • Determine the overall response rate (partial response, PR, or better) in these patients after 4, 8, and 12 courses of this regimen.
  • Determine the duration of progression-free and overall survival of patients treated with this regimen.
  • To evaluate the toxicity of this regimen in these patients.
  • To evaluate the ability to successfully collect peripheral blood stem cells from these patients after 4 months of this regimen.
  • To evaluate the CR or nCR rate in these patients after 8 and 12 courses of this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral cyclophosphamide on days 1, 8, 15, and 22; bortezomib IV on days 1, 4, 8 , and 11 OR days 1, 8, 15 and 22; and dexamethasone on days 1-4, 9-12, and 17-20 in courses 1 and 2 and days 1, 18, 15, and 22 in all subsequent courses. Courses repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma and Plasma Cell Neoplasm
  • Drug: bortezomib

    First 33 patients: 1.3 mg/m^2 IV Days 1, 4, 8 & 11

    Remaining 30 patients: 1.5 mg/m^2 IV Days 1, 8, 15 & 22

  • Drug: cyclophosphamide
    300mg/m^2 PO days 1, 8, 15 & 22
  • Drug: dexamethasone

    First 33 patients: 40 mg PO Days 1-4, 9-12, 17-20

    Remaining 30 patients: 40 mg PO Days 1-4, 9-12, 17-20 for cycles 1-2; Days 1, 8, 15, 22 for cycle 3+2 for cycle 3 and beyond

Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
63
November 2010
January 2009   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Confirmed diagnosis of symptomatic multiple myeloma

    • Durie Salmon stage 2 or higher
    • Previously untreated multiple myeloma (including immunomodulatory drugs such as thalidomide) with the exception of bisphosphonates
  • Evaluable or measurable disease, as defined by at least one of the following:

    • Serum monoclonal protein ≥ 1 g/dL (measurable disease)
    • Urine monoclonal protein ≥ 200 mg/24 hours by protein electrophoresis (measurable disease)
    • Serum-free light chains (FLC) ≥ 10 mg/dL, kappa or lambda, accompanied by an abnormal kappa/lambda ratio

Serum FLC's should only be used for patients without measurable serum or urine m-spike

- Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)

* Patients diagnosed with smoldering myeloma or monoclonal gammopathy of undetermined significance are not eligible

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2

    - ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator

  • Total bilirubin normal OR direct bilirubin ≤ 2.0 mg/dL
  • Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN
  • Creatinine ≤ 3.5 mg/dL
  • Absolute neutrophil count ≥ 1,000/mm³ without transfusion or growth factor
  • Platelet count ≥ 100,000/mm³ without transfusion or growth factor
  • Willingness and the physical and mental capability to provide written informed consent
  • Willingness to return to Mayo Clinic Arizona/Princess Margaret Hospital for follow-up
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

Exclusion criteria:

  • Peripheral sensory neuropathy ≥ grade 2 as defined by National Cancer Institute (NCI) Common Terminology for Common Adverse Events (CTCAE) version 3.0
  • Known hypersensitivity to compounds containing boron or mannitol
  • Active uncontrolled infection
  • Severe cardiac comorbidity including but not limited to:

    • New York Heart Association class III or IV heart failure
    • History of myocardial infarction within the past 6 months
    • Uncontrolled angina or electrocardiographic (ECG) evidence of acute ischemia
    • Severe uncontrolled ventricular arrhythmias or ECG evidence of active conduction system abnormalities
    • Cardiac amyloidosis with hypotension (i.e., systolic blood pressure < 100 mm Hg)
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent study compliance or completion of study treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior high-dose corticosteroid therapy for 12 days or less is permitted for emergent complications from newly diagnosed multiple myeloma
  • More than 14 days since prior investigational agents
  • No concurrent steroids or any other anticancer agents or treatments

    - Patients may receive the equivalent of up to 20 mg prednisone per day for concurrent illness or adrenal replacement therapy

  • Concurrent palliative radiotherapy for bony pain or fracture is allowed
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00609167
CDR0000583225, P30CA015083, MC0686, 06-002613, NCI-2010-02147
Yes
Alexander Keith Stewart, M.B.Ch.B, Mayo Clinic Cancer Center
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: A. Keith Stewart, M.B., Ch.B. Mayo Clinic
Mayo Clinic
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP