Bortezomib Based Consolidation in Multiple Myeloma Patients Completing Stem Cell Transplant

Phase 2

Completed

Conditions: Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma

Interventions: Drug: bortezomib
Drug: lenalidomide
Other: laboratory biomarker analysis
Drug: cyclophosphamide
Procedure: quality-of-life assessment
Drug: dexamethasone

Registration Number: NCT01706666

Lead Sponsor: Mayo Clinic

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C (bortezomib, lenalidomide)	lenalidomide	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Arm A (bortezomib)	laboratory biomarker analysis	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.
Arm A (bortezomib)	quality-of-life assessment	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.
Arm B (bortezomib, cyclophosphamide, dexamethasone)	laboratory biomarker analysis	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.
Arm B (bortezomib, cyclophosphamide, dexamethasone)	quality-of-life assessment	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.
Arm C (bortezomib, lenalidomide)	laboratory biomarker analysis	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Arm C (bortezomib, lenalidomide)	quality-of-life assessment	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Arm C (bortezomib, lenalidomide)	bortezomib	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Arm B (bortezomib, cyclophosphamide, dexamethasone)	bortezomib	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.
Arm A (bortezomib)	bortezomib	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.
Arm B (bortezomib, cyclophosphamide, dexamethasone)	cyclophosphamide	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.
Arm B (bortezomib, cyclophosphamide, dexamethasone)	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months	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.

Secondary Outcome Measures

Name	Time	Method
Survival Time	From registration to death due to any cause, assessed up to 3 years	The distribution of survival time will be estimated by arm using the method of Kaplan-Meier.
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	The distribution of progression-free survival will be estimated by arm using the method of Kaplan-Meier.

Trial Locations

Locations (4): Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Baylor Medical Center
🇺🇸
Garland, Texas, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States