Bortezomib Based Consolidation in Multiple Myeloma Patients Completing Stem Cell Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01706666
First received: October 11, 2012
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

This randomized phase II trial studies how well giving bortezomib with or without combination chemotherapy works as consolidation therapy in patients with newly diagnosed multiple myeloma who have completed 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 cyclophosphamide, dexamethasone, and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving bortezomib is more effective with or without combination chemotherapy in the post transplant setting.


Condition Intervention Phase
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: bortezomib
Drug: cyclophosphamide
Drug: lenalidomide
Other: laboratory biomarker analysis
Drug: dexamethasone
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized Study of Three Subcutaneous Bortezomib-based Consolidation Treatments for Patients Completing Induction Therapy and Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Proportion of patients experiencing a stringent complete response (sCR) after 12 cycles 24 months [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Estimated by the number of sCRs divided by the total number of evaluable patients in each arm. Exact binomial confidence intervals for the true sCR rate will be calculated by arm.


Secondary Outcome Measures:
  • Survival time [ Time Frame: From registration to death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated by arm using the method of Kaplan-Meier.

  • Progression-free survival [ Time Frame: From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    The distribution of progression-free survival will be estimated by arm using the method of Kaplan-Meier.

  • Incidence of adverse events, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    The maximum grade for each type of adverse event and relationship will be recorded for each patient, and frequency tables will be reviewed to determine patterns by arm.


Estimated Enrollment: 150
Study Start Date: December 2012
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (bortezomib)
Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.
Drug: bortezomib
Given SC
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm B (bortezomib, cyclophosphamide, dexamethasone)
Patients receive bortezomib SC as in Arm A, cyclophosphamide PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.
Drug: bortezomib
Given SC
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: cyclophosphamide
Given PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Other: laboratory biomarker analysis
Correlative studies
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm C (bortezomib, lenalidomide)
Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Drug: bortezomib
Given SC
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the stringent complete response (sCR) rate after 12 cycles among arms.

SECONDARY OBJECTIVES:

I. To compare progression-free and overall survival among arms. II. To describe the adverse event profile of each arm.

TERTIARY OBJECTIVES:

I. To compare sCR after 6 cycles and 24 cycles and quality of life among arms.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A: Patients receive bortezomib subcutaneously (SC) on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.

ARM B: Patients receive bortezomib SC as in Arm A, cyclophosphamide orally (PO) on days 1 and 15 of courses 1-12 and day 1 of courses 13-24, and dexamethasone PO on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.

ARM C: Patients receive bortezomib SC as in Arm A and lenalidomide PO once daily (QD) on days 1-28.

In all arms, treatment continues every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 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:

  • Creatinine =< 2 mg/dL
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelet count >= 75000/mm^3
  • Hemoglobin >= 8.0 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Treated myeloma: Prior induction therapy (any) and followed by autologous stem cell transplantation
  • Measurable disease at initial diagnosis, pre-stem cell transplant (SCT) or post-SCT of multiple myeloma as defined by at least ONE of the following:

    • Serum monoclonal protein >= 0.5 g/dL
    • > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
    • Serum immunoglobulin free light chain >= 5 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
    • Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • < 120 days post SCT with no evidence of relapse or progression prior to registration
  • Provide voluntary informed written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Willing to return to enrolling institution for follow-up during the active monitoring phase of the study
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Female patients who:

    • Are postmenopausal for at least 1 year before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse
  • Male patients, even if surgically sterilized (ie, status postvasectomy), who:

    • Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study treatment, OR
    • Agree to completely abstain from heterosexual intercourse

Exclusion Criteria:

  • Other active malignancy =< 3 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
  • Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
  • Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
  • Known to be human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus positive (HBV+)
  • Hypersensitivity to study drugs, boron or mannitol
  • Patient refractory to bortezomib (defined as patients who progressed while on bortezomib or within 60 days of receiving bortezomib)
  • Any serious medical or psychiatric condition that would prevent the subject from complying with the protocol treatment and procedures
  • Grade >= 2 peripheral neuropathy
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial
  • Radiation therapy within 3 weeks before randomization; enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy
  • Female patients who are lactating or pregnant
  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: NCT01706666

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Texas
Baylor Medical Center
Garland, Texas, United States, 75042
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Craig B. Reeder, M.D. Mayo Clinic in Arizona
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01706666     History of Changes
Other Study ID Numbers: MC1186, NCI-2012-01579
Study First Received: October 11, 2012
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Maintenance
Consolidation

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
Cyclophosphamide
Lenalidomide
Bortezomib
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014