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

NCT00609167 | Completed Phase 2 Results DMC

• 5 other identifiers: CDR0000583225P30CA015083MC068606-002613NCI-2010-02147
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 2

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  After 4 months of treatment

Secondary Outcomes (8)

• Progression Free Survival (PFS)

  up to 5 years

• Overall Survival (OS)

  From date of registration until death (up to 5 years)

• 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

  4 cycles

• Duration of Response

  Duration of study (up to 12 cycles)

• Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 8 Cycles

  After 8 cycles of treatment

Interventions

bortezomib DRUG

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

cyclophosphamide DRUG

300mg/m\^2 PO days 1, 8, 15 \& 22

dexamethasone DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259-5499, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2N9, Canada

Location

Related Publications (2)

• 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.

  PMID: 19225538 RESULT

• 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.

  PMID: 20413666 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; Cyclophosphamide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. A. Keith Stewart
• Organization: Mayo Clinic

stewart.keith@mayo.edu

Study Officials

• A. Keith Stewart, M.B., Ch.B.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 6, 2008
• Study Start: December 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: November 1, 2010
• Last Updated: May 17, 2011
• Results First Posted: December 7, 2010

Record last verified: 2011-05

Locations

CA (1); US (1)