Response Adapted Therapy With Bortezomib/Dexamethasone Followed by Addition of Lenalidomide in Non Responders as Initial Treatment for Patients With Multiple Myeloma

NCT01919086 | Completed Phase 2 Results

• 1 other identifier: 13-064
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to see if researchers could get the same good results with less toxicity by using this new approach. We already know that the three drugs bortezomib, lenalidomide, and dexamethasone given together at the same time are effective. Most physicians therefore treat patients with multiple myeloma with the 3 drug combination. However, the researchers also know that the three drugs given together result in more side effects than when only 2 drugs (bortezomib and dexamethasone or lenalidomide and dexamethasone) are given. The researchers believe that all patients may not necessarily need the three drugs to have good results. In this study, the researchers will first treat your disease with bortezomib and dexamethasone. If the disease is not well controlled with these 2 drugs, only then the third drug, lenalidomide, will be added. By using this sequential approach we may reach the same good results with fewer side effects.

Conditions

Multiple Myeloma (MM)

Keywords

Bortezomib; Dexamethasone; Lenalidomide; 13-064

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  (defined as \> or = to PR) after 4 cycles of response-adapted sequential therapy, using bortezomib and dexamethasone (BD) followed by the addition of lenalidomide in suboptimal responders

  after 4 cycles of response-adapted sequential therapy, up to 5 months

Secondary Outcomes (4)

• Overall Response Rate

  after 8 cycles of response-adapted sequential therapy, up to 9 months

• Response

  Up to eight cycles of treatment, up to 9 months

• Number of Participants Evaluated for Toxicity

  2 years

• Progression-free Survival (PFS)

  Up to 7 years

Other Outcomes (3)

• Characterization of Genomic Mutations of Targetable Genes

  2 years

• Characterization of Immunomodulatory Checkpoint Pathways in Multiple Myeloma

  2 years

• Quality of Life (QOL)

  2 years

Study Arms (1)

Patients with Multiple Myeloma

EXPERIMENTAL

This is a phase II, single center clinical trial designed to evaluate the response rate and toxicity of a response-adapted, sequential therapy, using bortezomib and dexamethasone, followed by the addition of lenalidomide in non-responders, in patients with untreated MM.

Drug: Bortezomib; Drug: Dexamethasone; Drug: Lenalidomide

Interventions

Bortezomib DRUG

Bortezomib SC (or IV if SC not tolerated) 1.5 mg/m\^2, days 1, 8, 15 and 22

Patients with Multiple Myeloma

Dexamethasone DRUG

Dexamethasone 40 mg PO or IV days 1, 4, 8,15 and 22 or on a split-dose regimen. (20mg BIW).

Patients with Multiple Myeloma

Lenalidomide DRUG

Lenalidomide may be added to the patient's regimen at any time if there is evidence of hematologic disease progression

Patients with Multiple Myeloma

Eligibility Criteria

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

You may qualify if:

• Age 18 or greater at the time of signing the informed consent document.
• Patients diagnosed with symptomatic multiple myeloma based on IMWG Diagnostic Criteria. According to these criteria, patient must have
• Monoclonal plasma cells in the bone marrow ≥ 10% and/or presence of a biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events:
• Clonal bone marrow plasma cell percentage ≥ 60% (Note: clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate, the highest value should be used)
• Involved:Uninvolved serum free light chain ratio ≥ 100 (values are based on the serum Freelite assay) The involved free light chain must be ≥ 10 mg/dL \>1 focal lesions on MRI studies (each focal lesion must be 5 mm or more in size)
• \[C\] Calcium elevation in the blood, defined as serum calcium \>11 mg/dl or \> 1 mg/dL higher than the upper limit of normal
• \[R\] Renal insufficiency, defined as serum creatinine \> 2 mg/dl or creatinine clearance \< 40 mL/min
• \[A\] Anemia, defined as hemoglobin \<10 g/dl or \> 2 g/dl below the lower limit of normal
• \[B\] Lytic bone lesions or osteoporosis. one or more osteolytic lesions on skeletal radiography, CT, or PET-CT (if bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement)
• Patients must have symptomatic multiple myeloma without advanced organ damage (such as multiple fractures or advanced bone disease causing immobilization, renal failure, spinal cord compression, or organ compromise due to soft tissue plasmacytoma). If immediate therapy with radiation and high-dose steroids (eg, for spinal cord compression) or if triple therapy is clearly advisable from the start, the patient is not eligible for this trial.
• Patients with measurable disease defined as one or more of the following: serum M protein ≥ 1.0 g/dl, urine M-protein ≥ 200 mg/24h, and/or serum FLC assay: involved FLC level ≥ 10 mg/dl with abnormal serum FLC ratio.
• Only non transplant candidates or those who opt to forgo ASCT during first line therapy are eligible
• ECOG performance status ≤ 2
• Female patients must:
• be postmenopausal for at least 1 year before the Screening visit, OR

You may not qualify if:

• Participant treated with any prior systemic therapy with the exception of the following:
• Treatment by localized radiotherapy for a specific indication within 2 weeks of initiation of treatment.
• Treatment with corticosteroids, not to exceed the equivalent of 160 mg of dexamethasone over a four-week period before initiation of protocol therapy.
• Presence of Primary or associated amyloidosis (AL)
• Participants who plan to proceed with ASCT as part of first line therapy
• Poor tolerability or known allergy to lenalidomide, bortezomib and/or dexamethasone or compounds that have similar chemical or biologic composition to these study drugs.
• Platelet count \< 50,000/mm3 within 21 days of initiation of protocol therapy for patients in whom \<50% of bone marrow nucleated cells are plasma cells; or platelet count \<30,000/mm3 for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells. Transfusion is not allowed to meet platelet eligibility criteria.
• ANC \< 1,000 cells/mm3 within 21 days of initiation of protocol therapy. Growth factor administration is not allowed to meet ANC eligibility criteria.
• Hemoglobin \< 8 g/dL within 21 days of initiation of protocol therapy. Transfusion may be used to meet hemoglobin eligibility criteria.
• Hepatic impairment, defined as bilirubin \> 1.5 x institutional upper limit of normal (ULN) Patients with benign hyperbilirubinemia (e.g., Gilbert's syndrome) are eligible or AST (SGOT), or ALT (SGPT), or alkaline phosphatase ≥ to 2 x ULN, within 21 days of initiation of protocol therapy.
• Renal insufficiency, defined as creatinine clearance \< 30 ml/min within 21 days of initiation of protocol therapy. Creatinine clearance will be the primary eligibility criteria in determining renal insufficiency. The Cockcroft-Gault formula.
• Active hepatitis B or C infection
• HIV 1 or 2 positivity
• Female participant who is pregnant or breast-feeding.
• Inability to comply with an anti-thrombotic treatment regimen (e.g., administration of aspirin, enoxaparin, or low molecular weight heparin administration).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Hartford Hospital: collaborator

Study Sites (7)

Hartford Healthcare Cancer Institute @ Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone; Lenalidomide

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Hani Hassoun, MD
• Organization: Memorial Sloan Kettering Cancer Center

hassounh@mskcc.org

646-608-3718

Study Officials

• Hani Hassoun, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 8, 2013
• Study Start: August 6, 2013
• Primary Completion: May 16, 2024
• Study Completion: May 16, 2024
• Last Updated: March 2, 2026
• Results First Posted: March 2, 2026

Record last verified: 2024-05

Locations

US (7)