Bortezomib Based Consolidation in Multiple Myeloma Patients Completing Stem Cell Transplant

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01706666
• Collaborator: (none)
• Enrollment: 3
• Locations: 4
• Arms: 3
• Actual Duration (Months): 41.3
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	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

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

TERTIARY OBJECTIVES:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Actual Study Start Date: Dec 7, 2012
• Actual Primary Completion Date: Jul 10, 2014
• Actual Study Completion Date: May 17, 2016

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: quality of life assessment

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Johns Hopkins University	Baltimore	Maryland	United States	21287-8936
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
4	Baylor Medical Center	Garland	Texas	United States	75042

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Craig B. Reeder, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01706666
• Other Study ID Numbers: MC1186; NCI-2012-01579
• First Posted: Oct 15, 2012
• Last Update Posted: Sep 17, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by Mayo Clinic: Maintenance; Consolidation
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Cyclophosphamide; Lenalidomide; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.	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.	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Period Title: Overall Study
STARTED	1	1	1
COMPLETED	1	1	1
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Arm A	Arm B	Arm C	Total
Arm/Group Description	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.	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.	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.	Total of all reporting groups
Overall Participants	1	1	1	3
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	54	45	50	50
Sex: Female, Male (Count of Participants)
Female	0 0%	1 100%	1 100%	2 66.7%
Male	1 100%	0 0%	0 0%	1 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	1 100%	1 100%	3 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 100%	0 0%	1 33.3%
White	1 100%	0 0%	1 100%	2 66.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	1 100%	3 100%
Had Prior Treatment (participants) [Number]
Number [participants]	1 100%	1 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.	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.	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Measure Participants	1	1	1
Number [percentage of participants]	100 10000%	0 0%	100 10000%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients are still alive

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.	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.	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Measure Participants	1	1	1
Number [Months to death]	NA	NA	NA

3. Secondary Outcome

Title	Progression-free Survival
Description	The distribution of progression-free survival will be estimated by arm using the method of Kaplan-Meier.
Time Frame	From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A	Arm B	Arm C
Arm/Group Description	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.	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.	Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
Measure Participants	1	1	1
Number [Months to Progression]	NA	9.2	NA

Adverse Events

Arm/Group Title	Arm A		Arm B		Arm C
Arm/Group Description	Patients receive bortezomib SC on days 1 and 15 of courses 1-12 and day 1 of courses 13-24.		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.		Patients receive bortezomib SC as in Arm A and lenalidomide PO QD on days 1-28.
All Cause Mortality
	Arm A		Arm B		Arm C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A		Arm B		Arm C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/1 (0%)		1/1 (100%)
Investigations
Neutrophil count decreased	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	1
Vascular disorders
Hypertension	1/1 (100%)	1	0/1 (0%)	0	0/1 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A		Arm B		Arm C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Anemia	1/1 (100%)	5	1/1 (100%)	10	0/1 (0%)	0
Gastrointestinal disorders
Constipation	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	10
Diarrhea	0/1 (0%)	0	1/1 (100%)	7	1/1 (100%)	2
Nausea	0/1 (0%)	0	1/1 (100%)	9	1/1 (100%)	2
Vomiting	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	1
General disorders
Fatigue	1/1 (100%)	1	1/1 (100%)	6	1/1 (100%)	13
Injection site reaction	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0
Malaise	1/1 (100%)	1	0/1 (0%)	0	0/1 (0%)	0
Investigations
Neutrophil count decreased	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	10
Platelet count decreased	1/1 (100%)	1	0/1 (0%)	0	1/1 (100%)	10
White blood cell decreased	0/1 (0%)	0	1/1 (100%)	5	1/1 (100%)	9
Nervous system disorders
Peripheral sensory neuropathy	1/1 (100%)	1	0/1 (0%)	0	1/1 (100%)	1
Renal and urinary disorders
Cystitis noninfective	1/1 (100%)	1	0/1 (0%)	0	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/1 (0%)	0	0/1 (0%)	0	1/1 (100%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.