Phase II Study of Efficacy and Safety of Lenalidomide, Subcutaneous Bortezomib and Dexamethasone Therapy for Newly Diagnosed Multiple Myeloma

NCT02441686 | Completed Phase 2 Results DMC

• 1 other identifier: 14-508
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 8

Brief Summary

This research study is evaluating a combination of three drugs called lenalidomide, subcutaneous (injection under the skin) bortezomib, and dexamethasone (RVD) as a possible treatment for multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• 4-Cycle Induction Overall Response Rate (ORR)

  4-cycle ORR was defined as the percentage of participants who achieved partial response or better based on the International Myeloma Working Group Response (IMWG) criteria during the first 4 cycles of induction therapy.

  Participants were followed up to 12 weeks.

• Induction Overall Response Rate (ORR)

  Induction ORR was defined as the percentage of participants who achieved partial response or better based on the International Myeloma Working Group Response (IMWG) criteria during induction therapy either 4 cycles or 8 cycles of combination therapy. Response on ASCT is not included.

  Participants were followed up to 24 weeks.

• Four-cycle Induction Peripheral Neuropathy (PN) Rate

  Four-cycle induction PN rate was defined as the proportion of participants who experienced peripheral neuropathy includes any attribution and any grades based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4) during the first 4 cycles of induction therapy.

  Participants were followed up to 12 weeks.

• Grade 3-4 Induction Peripheral Neuropathy Rate

  Grade 3-4 induction peripheral neuropathy rate was defined as the proportion of participants who experienced grade 3 or 4 peripheral neuropathy based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4) as reported on case report forms during induction therapy (4 cycles RsqVd for ASCT patients and 8 cycles for non-ASCT patients).

  Participants were followed up to 24 weeks.

Secondary Outcomes (4)

• Median Time to Progression (TTP)

  Disease was assessed up to 41.2 months.

• 1-Year Progression Free Survival (PFS) Probability

  Median follow up for PFS is 13.4 months with the relevant observation timepoint equal to 1 year.

• Median Duration of Response (DOR)

  Disease was assessed up to 41.2 months.

• 1-year Overall Survival (OS) Rate

  Survival was assessed up to 1 year.

Study Arms (1)

Lenalidomide, subcutaneous Bortezomib, Dexamethasone

EXPERIMENTAL

Lenalidomide (R): 25 mg on days 1-14 orally Subcutaneous Bortezomib (sqV): 1.3 mg/m\^2 on days 1, 4, 8 and 11 Dexamethasone (d): 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 Stem cell mobilization occurs at the end of Cycle 4. Participants may elect to stop treatment at the end of Induction Cycle 4 and proceed to autologous stem cell transplant (ASCT) with melphalan 200 mg/m\^2 conditioning, or receive a full 8 cycles of RsqVd induction therapy. RsqVd cycle duration is 21-days. Maintenance follows with the specific regimen determined by risk category. High-risk participants defined as those with International Staging System (ISS) stage II or stage III disease and/or high-risk cytogenetics including t(4;14), t(4; 16), del(17p) receive sqV of 1.3 mg/m\^2 on days 1 and 15 in addition to R 10mg (15mg after cycle 3 if tolerated) on days 1-21 of 28-day cycle. Standard-risk participants receive R monotherapy.

Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Procedure: Stem Cell Mobilization; Procedure: Autologous Stem Cell Transplant

Interventions

Bortezomib DRUG

Also known as: Velcade®

Lenalidomide, subcutaneous Bortezomib, Dexamethasone

Lenalidomide DRUG

Also known as: Revlimid®

Lenalidomide, subcutaneous Bortezomib, Dexamethasone

Dexamethasone DRUG

Also known as: Decadron, Dexasone, Diodex, Hexadrol, Maxidex

Lenalidomide, subcutaneous Bortezomib, Dexamethasone

Stem Cell Mobilization PROCEDURE

Lenalidomide, subcutaneous Bortezomib, Dexamethasone

Autologous Stem Cell Transplant PROCEDURE

Also known as: ASCT

Lenalidomide, subcutaneous Bortezomib, Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Diagnosis of symptomatic MM, according to International Myeloma Foundation 2003 Diagnostic Criteria:
• Clonal plasma cells \>10% on bone marrow biopsy
• A monoclonal protein (paraprotein) in either serum or urine(except in cases of non-secretory myeloma)\*
• Myeloma-related organ dysfunction (1 or more) of the following (evidence of end-organ damage felt related to the plasma cell disorder related organ or tissue impairment (ROTI), commonly referred to by the acronym "CRAB"):
• Serum Ca ≥ 10.5 mg/dL or
• Renal insufficiency attributable to myeloma. Serum creatinine \> 2mg/dL
• Anemia: Normochromic, normocytic with a hemoglobin value \> 2g/dL below the lower limit of normal or a hemoglobin \<10 g/dL
• Bone lesions (lytic lesions, severe osteopenia or pathologic fractures) or osteoporosis. \*If no monoclonal protein is detected (non-secretory disease), then \>/= 30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma required.
• Has received no prior treatment with any systemic therapy for the treatment of multiple myeloma
• Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period).
• Bisphosphonates are permitted.
• Local radiation as long as two weeks have lapsed since last date of radiotherapy, which is recommended to be a limited field.
• Age ≥18 years at the time of signing Informed Consent
• ECOG performance status ≤ 2 (Karnofsky ≥ 50%)
• Voluntary written informed consent

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Renal insufficiency (serum creatinine levels \> 2.5 mg/dL, calculated Crcl with Cockcroft-Gault formula, see Appendix B, \< 45 ml/min)
• Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count ≥ 50,000 cells/mm3)
• Subjects with an absolute neutrophil count (ANC) \< 1000 cells/mm3. Growth factors may not be used to meet ANC eligibility criteria
• Subjects with a hemoglobin \< 8.0 g/dL
• AST (SGOT) and ALT (SGPT) \> 2 x institutional ULN, bilirubin levels ≥1.5 institutional ULN
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix C), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Clinically relevant active infection requiring treatment (antibiotics, antivirals, antifungals).
• Any serious co-morbid condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study.
• Female subject is pregnant or breast-feeding.
• Serious psychiatric illness or addiction likely to interfere with participation in this clinical study.
• Uncontrolled diabetes mellitus.
• Contraindication to any required concomitant drugs or supportive therapies including hypersensitivity to all anticoagulation and antiplatelet options or hypersensitivity to acyclovir or similar anti-viral drug.
• History of allergic reaction/hypersensitivity attributed to compounds containing boron, mannitol, polysorbate 80 or sodium citrate dehydrate.
• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Celgene: collaborator

Study Sites (8)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Eastern Maine Medical Center

Brewer, Maine, 04412, United States

Location

Massachusetts General Hosptial

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Virginia Piper Cancer Institute

Coon Rapids, Minnesota, 55433, United States

Location

Virgina Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Hematology Oncology of Northern New Jersey

Morristown, New Jersey, 07962, United States

Location

Related Publications (1)

• O'Gorman P, Laubach JP, O'Dwyer ME, Krawczyk J, Yee AJ, Gilligan O, Cahill MR, Rosenblatt J, Quinn J, Murphy PT, DiPietro H, Perera MR, Crotty GM, Cummings K, Hayden PJ, Browne P, Savell A, O'Leary HM, O'Keeffe D, Masone K, Hennessy BJ, Guerrero Garcia T, Scott K, Saeed K, Bianchi G, Dowling P, Tierney C, Richardson PG. Phase 2 studies of lenalidomide, subcutaneous bortezomib, and dexamethasone as induction therapy in patients with newly diagnosed multiple myeloma. Am J Hematol. 2022 May;97(5):562-573. doi: 10.1002/ajh.26491. Epub 2022 Feb 18.

  PMID: 35132679 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Lenalidomide; Dexamethasone; Calcium Dobesilate; Hematopoietic Stem Cell Mobilization

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; 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; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Biological Therapy; Therapeutics

Results Point of Contact

• Title: Emily Benjamin
• Organization: Dana-Farber Cancer Institute

emily_benjamin@dfci.harvard.edu

6176324167

Study Officials

• Jacob Laubach

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 8, 2015
• First Posted: May 12, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2021
• Study Completion: October 1, 2025
• Last Updated: January 13, 2026
• Results First Posted: March 4, 2024

Record last verified: 2025-12

Locations

US (8)