Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65 (DFCI 10-106)
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| ClinicalTrials.gov Identifier: NCT01208662 |
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Recruitment Status :
Active, not recruiting
First Posted : September 24, 2010
Last Update Posted : April 19, 2023
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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 |
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| Multiple Myeloma | Drug: Lenalidomide Drug: Bortezomib Drug: Dexamethasone Procedure: Autologous Stem Cell Transplant | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Estimated 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 : | October 2010 |
| Actual Primary Completion Date : | June 2022 |
| Estimated Study Completion Date : | September 2025 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: High Dose Treatment
Lenalidomide, bortezomib, dexamethasone. Stem cell collection. Maintenance Lenalidomide.
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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 Name: 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:
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 Name: Decadron |
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Experimental: High Dose Treatment with SCT
Lenalidomide, bortezomib, dexamethasone. Stem cell collection. Autologous Stem Cell Transplant. Maintenance Lenalidomide.
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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 Name: 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:
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 Name: Decadron Procedure: Autologous Stem Cell Transplant Stem cell transplant |
- Primary Outcome [ Time Frame: Up to 6 years or until progression ]To compare progression-free survival (PFS) between Arm A and Arm B.
- Secondary Outcome [ Time Frame: Up to 6 years or until progression ]To compare the response rates (RR) between the two arms.
- Secondary Outcome [ Time Frame: Up to 6 years or until progression ]To compare time to progression (TTP) between the two arms.
- Secondary Outcome [ Time Frame: Up to 6 years or until progression ]To compare the overall survival (OS) between the two arms.
- Secondary Outcome [ Time Frame: Up to 6 years or until progression ]To compare toxicity between the two arms.
- Secondary Outcome [ Time Frame: Up to 6 years or until progression ]To define genetic prognostic groups evaluated by gene expression profiling (GEP).
- Secondary Outcomes [ Time Frame: Up to 6 years or until progression ]To examine the best treatment in each GEP-defined prognostic group.
- Secondary Outcome [ Time Frame: Up to 6 years or until progression ]To compare quality of life (QOL) between the two arms.
- Secondary Outcome [ Time Frame: Up to 6 years or until progression ]To collect medical resource utilization (MRU) information which may be used in economic evaluation models.
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01208662
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| Principal Investigator: | Paul G. Richardson, MD | Dana-Farber Cancer Institute |
| Responsible Party: | Paul Richardson, MD, Principal Investigator, Dana-Farber Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT01208662 |
| Other Study ID Numbers: |
10-106 |
| First Posted: | September 24, 2010 Key Record Dates |
| Last Update Posted: | April 19, 2023 |
| Last Verified: | April 2023 |
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Lenalidomide Bortezomib Dexamethasone |
Stem Cell Transplant Myeloma Multiple Myeloma |
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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 Dexamethasone |
Lenalidomide Bortezomib Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors Angiogenesis Inhibitors |