DFCI 10-106: Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65

Sponsor

Paul G. Richardson, MD (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01208662

Collaborator

Celgene Corporation (Industry), Millennium Pharmaceuticals, Inc. (Industry), Massachusetts General Hospital (Other), Cape Cod Hospital (Other), Beth Israel Deaconess Medical Center (Other), Emory University (Other), University of Michigan (Other), Fox Chase Cancer Center (Other), Memorial Sloan Kettering Cancer Center (Other), Fred Hutchinson Cancer Center (Other), Barbara Ann Karmanos Cancer Institute (Other), Duke University (Other), University of California, San Francisco (Other), University of Chicago (Other), M.D. Anderson Cancer Center (Other), UNC Lineberger Comprehensive Cancer Center (Other), Roswell Park Cancer Institute (Other), Stanford University (Other), University of Mississippi Medical Center (Other), Icahn School of Medicine at Mount Sinai (Other), Wake Forest University Health Sciences (Other), University of Arizona (Other), OHSU Knight Cancer Institute (Other), Eastern Maine Medical Center (Other), University of California, San Diego (Other), University of Alabama at Birmingham (Other), University of Pittsburgh Medical Center (Other), Ochsner Health System (Other), University of Texas Southwestern Medical Center (Other), State University of New York - Downstate Medical Center (Other), Newton-Wellesley Hospital (Other), Baylor College of Medicine (Other), City of Hope Medical Center (Other), University of Florida (Other), Northwell Health (Other), H. Lee Moffitt Cancer Center and Research Institute (Other), Vanderbilt University Medical Center (Other), Ohio State University (Other), Huntsman Cancer Institute (Other), Columbia University (Other)

660

Enrollment

Locations

Arms

167

Anticipated Duration (Months)

14.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The drugs, lenalidomide, bortezomib, and dexamethasone, are approved by the FDA. They have not been approved in the combination for multiple myeloma or any other type of cancer. Bortezomib is currently approved by the FDA for the treatment of multiple myeloma. Lenalidomide is approved for use with dexamethasone for patients with multiple myeloma who have received at least one prior therapy and for the treatment of certain types of myelodysplastic syndrome (another type of cancer affecting the blood). Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Please note that Bortezomib and Lenalidomide are provided to patients participating in this trial at no charge. Melphalan and cyclophosphamide, the drugs used during stem cell collection and transplant, are also approved by the FDA. Melphalan is an FDA-approved chemotherapy for multiple myeloma and is used as a high-dose conditioning treatment prior to stem cell transplantation. Cyclophosphamide is used, either alone, or in combination with other drugs, to treat multiple myeloma. These drugs have been used in other multiple myeloma studies and information from those studies suggests that this combination of therapy may help to treat newly diagnosed multiple myeloma.

In this research study, we are looking to explore the drug combination, lenalidomide, bortezomib and dexamethasone alone or when combined with autologous stem cell transplantation to see what side effects it may have and how well it works for treatment of newly diagnosed multiple myeloma. Specifically, the objective of this trial is to determine if, in the era of novel drugs, high dose therapy (HDT) is still necessary in the initial management of multiple myeloma in younger patients. In this study, HDT as compared to conventional dose treatment would be considered superior if it significantly prolongs progression-free survival by at least 9 months or more, recognizing that particular subgroups may benefit more compared to others.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Lenalidomide Drug: Bortezomib Drug: Dexamethasone Procedure: Autologous Stem Cell Transplant	Phase 3

Detailed Description

After screening procedures determine if a patient is eligible for this research study, the patient will be randomized into one of the study groups: lenalidomide, bortezomib and dexamethasone without autologous stem cell transplantation, followed by lenalidomide maintenance (Arm A) or lenalidomide, bortezomib and dexamethasone with autologous stem cell transplantation, followed by lenalidomide maintenance (Arm B). There is an equal chance of being placed in either group.

All participants will receive one cycle of lenalidomide, bortezomib and dexamethasone treatment before being randomized to Arm A or Arm B.

Participants in Arm A will receive two additional cycles of lenalidomide, bortezomib and dexamethasone prior to stem cell collection. If randomized to Arm A, the subject will undergo stem cell collection, followed by five cycles of lenalidomide, bortezomib and dexamethasone. This will be followed by lenalidomide maintenance treatment until disease progression.

Participants in Arm B will receive two additional cycles of lenalidomide, bortezomib and dexamethasone prior to stem cell collection. If randomized to Arm B, the subject will undergo stem cell collection and autologous stem cell transplantation, followed by two cycles of lenalidomide, bortezomib and dexamethasone. This will be followed by lenalidomide maintenance treatment until disease progression.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

660 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Phase III Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib, and Dexamethasone (RVD) to High-Dose Treatment With Peripheral Stem Cell Transplant in the Initial Management of Myeloma in Patients Up to 65 Years of Age

Actual Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Feb 1, 2022

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: High Dose Treatment Lenalidomide, bortezomib, dexamethasone. Stem cell collection. Maintenance Lenalidomide.	Drug: Lenalidomide Oral, 25 mg/day, days 1-14 for 8 total cycles for Arm A. Oral, 25 mg/day, days 1-14 for 5 total cycles for Arm B. Oral, 10-15 mg/day, daily for 12 months in maintenance for Arm A and Arm B. Other Names: CC-5013 Drug: Bortezomib IV, days 1, 4, 8 and 11 for 8 total cycles for Arm A. IV, days 1, 4, 8 and 11 for 5 total cycles for Arm B. Other Names: PS-341 Velcade Drug: Dexamethasone Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 8 total cycles for Arm A. Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 5 total cycles for Arm B. Dose of 20 mg/day for first 3 cycles. Dose of 10 mg/day for remaining cycles. Other Names: Decadron
Experimental: High Dose Treatment with SCT Lenalidomide, bortezomib, dexamethasone. Stem cell collection. Autologous Stem Cell Transplant. Maintenance Lenalidomide.	Drug: Lenalidomide Oral, 25 mg/day, days 1-14 for 8 total cycles for Arm A. Oral, 25 mg/day, days 1-14 for 5 total cycles for Arm B. Oral, 10-15 mg/day, daily for 12 months in maintenance for Arm A and Arm B. Other Names: CC-5013 Drug: Bortezomib IV, days 1, 4, 8 and 11 for 8 total cycles for Arm A. IV, days 1, 4, 8 and 11 for 5 total cycles for Arm B. Other Names: PS-341 Velcade Drug: Dexamethasone Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 8 total cycles for Arm A. Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 5 total cycles for Arm B. Dose of 20 mg/day for first 3 cycles. Dose of 10 mg/day for remaining cycles. Other Names: Decadron Procedure: Autologous Stem Cell Transplant Stem cell transplant

Arm

Intervention/Treatment

Active Comparator: High Dose Treatment

Lenalidomide, bortezomib, dexamethasone. Stem cell collection. Maintenance Lenalidomide.

Drug: Lenalidomide

Oral, 25 mg/day, days 1-14 for 8 total cycles for Arm A. Oral, 25 mg/day, days 1-14 for 5 total cycles for Arm B. Oral, 10-15 mg/day, daily for 12 months in maintenance for Arm A and Arm B.

Other Names:

CC-5013

Drug: Bortezomib

IV, days 1, 4, 8 and 11 for 8 total cycles for Arm A. IV, days 1, 4, 8 and 11 for 5 total cycles for Arm B.

Other Names:

PS-341

Velcade

Drug: Dexamethasone

Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 8 total cycles for Arm A. Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 5 total cycles for Arm B. Dose of 20 mg/day for first 3 cycles. Dose of 10 mg/day for remaining cycles.

Other Names:

Decadron

Experimental: High Dose Treatment with SCT

Lenalidomide, bortezomib, dexamethasone. Stem cell collection. Autologous Stem Cell Transplant. Maintenance Lenalidomide.

Drug: Lenalidomide

Oral, 25 mg/day, days 1-14 for 8 total cycles for Arm A. Oral, 25 mg/day, days 1-14 for 5 total cycles for Arm B. Oral, 10-15 mg/day, daily for 12 months in maintenance for Arm A and Arm B.

Other Names:

CC-5013

Drug: Bortezomib

IV, days 1, 4, 8 and 11 for 8 total cycles for Arm A. IV, days 1, 4, 8 and 11 for 5 total cycles for Arm B.

Other Names:

PS-341

Velcade

Drug: Dexamethasone

Other Names:

Decadron

Procedure: Autologous Stem Cell Transplant

Stem cell transplant

Outcome Measures

Primary Outcome Measures

Primary Outcome [Up to 6 years or until progression]
To compare progression-free survival (PFS) between Arm A and Arm B.

Secondary Outcome Measures

Secondary Outcome [Up to 6 years or until progression]
To compare the response rates (RR) between the two arms.
Secondary Outcome [Up to 6 years or until progression]
To compare time to progression (TTP) between the two arms.
Secondary Outcome [Up to 6 years or until progression]
To compare the overall survival (OS) between the two arms.
Secondary Outcome [Up to 6 years or until progression]
To compare toxicity between the two arms.
Secondary Outcome [Up to 6 years or until progression]
To define genetic prognostic groups evaluated by gene expression profiling (GEP).
Secondary Outcomes [Up to 6 years or until progression]
To examine the best treatment in each GEP-defined prognostic group.
Secondary Outcome [Up to 6 years or until progression]
To compare quality of life (QOL) between the two arms.
Secondary Outcome [Up to 6 years or until progression]
To collect medical resource utilization (MRU) information which may be used in economic evaluation models.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of Multiple Myeloma, according to the International Myeloma Foundation 2003 Diagnostic Criteria
Documented symptomatic myeloma, with organ damage related to myeloma with laboratory assessments performed within 21 days of registration
Myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains.
ECOG performance status </= 2
Negative HIV blood test
Voluntary written informed consent

Exclusion Criteria:

Pregnant or lactating female
Prior systemic therapy for MM (localized radiotherapy allowed if at least 7 days before study entry, corticosteroids allowed if dose </= equivalent of 160 mg dexamethasone over 2 weeks)
Primary amyloidosis (AL) or myeloma complicated by amylosis
Receiving any other investigational agents
Known brain metastases
Poor tolerability or allergy to any of the study drugs or compounds of similar composition
Platelet count <50,000/mm3, within 21 days of registration
ANC <1,000 cells/mm3, within 21 days of registration
Hemoglobin <8 g/dL, within 21 days of registration
Hepatic impairment (>/= 1.5 x institutional ULN or AST (SGOT), ALT (SGPT), or alkaline phosphatase >2 x ULN). Patients with benign hyperbilirubinemia are eligible.
Renal insufficiency (serum creatinine >2.0 mg/dl or creatinine clearance <50 ml/min, within 21 days of registration)
Respiratory compromise (DLCO < 50%)
Clinical signs of heart or coronary failure or LVEF < 40%. Myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conductive system abnormalities
Intercurrent illness including, but not limited to ongoing or active severe infection, known infection with hepatitis B or C virus, poorly controlled diabetes, severe uncontrolled psychiatric disorder or psychiatric illness/social situations that would limit compliance with study requirements
Previous history of another malignant condition except for basal cell carcinoma and stage I cervical cancer. If malignancy was experienced more than 2 years ago and confirmed as cured, these participants may be considered for the study on case by case basis with PI discussion.
Inability to comply with an anti-thrombotic treatment regimen
Peripheral neuropathy >/= Grade 2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Arizona Comprehensive Cancer Center	Tucson	Arizona	United States	85724
3	City of Hope	Duarte	California	United States	91010
4	University of California at San Diego	La Jolla	California	United States
5	University of California, San Francisco	San Francisco	California	United States	94143
6	Stanford University	Stanford	California	United States	94305
7	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
8	University of Florida	Gainesville	Florida	United States	32608
9	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
10	Emory University	Atlanta	Georgia	United States	30322
11	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
12	University of Chicago	Chicago	Illinois	United States	60637
13	Ochsner Foundation Clinic	New Orleans	Louisiana	United States	70121
14	Eastern Maine Medical Center	Brewer	Maine	United States	04412
15	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
16	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
17	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
18	Cape Cod Healthcare	Hyannis	Massachusetts	United States	02601
19	Newton-Wellesley Hospital	Newton	Massachusetts	United States
20	University of Michigan	Ann Arbor	Michigan	United States	48109
21	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
22	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
23	New Hampshire Oncology and Hematology	Concord	New Hampshire	United States
24	New Hampshire Oncology and Hematology	Hooksett	New Hampshire	United States
25	New Hampshire Oncology and Hematology	Laconia	New Hampshire	United States
26	State University of New York Downstate Medical Center	Brooklyn	New York	United States
27	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
28	North Shore Long Island Jewish Health System	Lake Success	New York	United States	11042
29	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
30	Mount Sinai Medical Center	New York	New York	United States	10029
31	Columbia University	New York	New York	United States	10032
32	University of Rochester Medical Center	Rochester	New York	United States	14642
33	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
34	Duke University	Durham	North Carolina	United States	27710
35	Wake Forest University	Winston-Salem	North Carolina	United States	27157
36	Ohio State University Medical Center	Columbus	Ohio	United States	43210
37	Oregon Health and Sciences	Portland	Oregon	United States
38	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States	19104
39	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
40	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
41	Vanderbilt University	Nashville	Tennessee	United States	37203
42	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
43	Baylor College of Medicine	Houston	Texas	United States	77030
44	MD Anderson Cancer Center	Houston	Texas	United States	77030
45	Huntsman Cancer Institute	Salt Lake City	Utah	United States
46	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109