Clinical trial NCT00609167: Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
Official title: A Phase II Trial of Cyclophosphamide, Bortezomib and Dexamethasone (CYBOR-D) in Patients With Newly Diagnosed Active Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-02-06
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
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
timeFrame: After 4 months of treatment
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: up to 5 years
measure: Overall Survival (OS)
timeFrame: From date of registration until death (up to 5 years)
measure: 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
timeFrame: 4 cycles
measure: Duration of Response
timeFrame: Duration of study (up to 12 cycles)
measure: Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 8 Cycles
timeFrame: After 8 cycles of treatment
measure: Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 12 Cycles
timeFrame: After 12 cycles of treatment
measure: Number of Participants With Severe Adverse Events
timeFrame: Every cycle during treatment (up to 12 cycles)
measure: Participants Who Successfully Completed Collection of Peripheral Blood Stem Cells for Transplant
timeFrame: After 4 cycles of treatment
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Mayo Clinic
name: A. Keith Stewart, M.B., Ch.B.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, Noble B, Pirooz NA, Spong JE, Piza JG, Zepeda VH, Mikhael JR, Leis JF, Bergsagel PL, Fonseca R, Stewart AK. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009 Jul;23(7):1337-41. doi: 10.1038/leu.2009.26. Epub 2009 Feb 19.
citation: Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Laumann K, Hentz J, Pirooz NA, Piza JG, Tiedemann R, Mikhael JR, Bergsagel PL, Leis JF, Fonseca R, Stewart AK. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood. 2010 Apr 22;115(16):3416-7. doi: 10.1182/blood-2010-02-271676. No abstract available.