Bortezomib Based Consolidation in Multiple Myeloma Patients Completing Stem Cell Transplant

NCT01706666 | Completed Phase 2 Results DMC

• 2 other identifiers: MC1186NCI-2012-01579
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Keywords

Maintenance; Consolidation

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months

  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. Stringent complete response (sCR) is defined as a complete response plus normal serum free light chain ratio and the absence of clonal cells in bone marrow by flow cytometry.

  24 months

Secondary Outcomes (2)

• Survival Time

  From registration to death due to any cause, assessed up to 3 years

• Progression-free Survival

  From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years

Study Arms (3)

Arm A (bortezomib)

EXPERIMENTAL

Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.

Drug: bortezomib; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Arm B (bortezomib, cyclophosphamide, dexamethasone)

EXPERIMENTAL

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; Drug: cyclophosphamide; Other: laboratory biomarker analysis; Drug: dexamethasone; Procedure: quality-of-life assessment

Arm C (bortezomib, lenalidomide)

EXPERIMENTAL

Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.

Drug: bortezomib; Drug: lenalidomide; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

Interventions

bortezomib DRUG

Given SC

Also known as: LDP 341, MLN341, VELCADE

Arm A (bortezomib); Arm B (bortezomib, cyclophosphamide, dexamethasone); Arm C (bortezomib, lenalidomide)

cyclophosphamide DRUG

Given PO

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Arm B (bortezomib, cyclophosphamide, dexamethasone)

lenalidomide DRUG

Given PO

Also known as: CC-5013, IMiD-1, Revlimid

Arm C (bortezomib, lenalidomide)

laboratory biomarker analysis OTHER

Correlative studies

Arm A (bortezomib); Arm B (bortezomib, cyclophosphamide, dexamethasone); Arm C (bortezomib, lenalidomide)

dexamethasone DRUG

Given PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Arm B (bortezomib, cyclophosphamide, dexamethasone)

quality-of-life assessment PROCEDURE

Ancillary studies

Also known as: quality of life assessment

Arm A (bortezomib); Arm B (bortezomib, cyclophosphamide, dexamethasone); Arm C (bortezomib, lenalidomide)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (4)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Baylor Medical Center

Garland, Texas, 75042, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Cyclophosphamide; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Craig B Reeder, MD
• Organization: Mayo Clinic Cancer Center

Reeder.Craig@mayo.edu

4803018335

Study Officials

• Craig B. Reeder, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2012
• First Posted: October 15, 2012
• Study Start: December 7, 2012
• Primary Completion: July 10, 2014
• Study Completion: May 17, 2016
• Last Updated: September 17, 2018
• Results First Posted: June 3, 2016

Record last verified: 2018-08

Locations

US (4)