Study of the Efficacy and Safety of RsqVD Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma

NCT02219178 | Completed Phase 2

• 2 other identifiers: CTRIAL-IE (ICORG) 13-172013-005008-32
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 8

Brief Summary

This study aims to evaluate the overall response rate after 4 cycles and the best response to induction therapy with combination of lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVD) in patients with newly diagnosed multiple myeloma.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• To evaluate the overall response rate (ORR) after 4 induction cycles

  To evaluate the overall response rate (ORR) after 4 induction cycles and the best response to induction therapy with the combination of lenalidomide, subcutaneous (SQ) bortezomib, and dexamethasone (RsqVD) in patients with newly diagnosed multiple myeloma.

  After 4 cycles (84 days)

Secondary Outcomes (4)

• a) To evaluate the rate and severity of Peripheral Neuropathy (PN) of SQ bortezomib in combination with lenalidomide, and dexamethasone after the 4th and after the final cycle of induction therapy.

  After 4 cycles (84 days)

• Progression of disease

  Duration of the study, expected to be approximately 3 years

• Progression free survival

  Duration of the study, expected to be approximately 3 years

• Duration of response

  Duration of the study, expected to be approximately 3 years

Study Arms (1)

RsqVD

EXPERIMENTAL

Oral lenalidomide 25mg days 1 - 14 of 21 day schedule Subcutaneous bortezomib 1.3mg/m2 days 1, 4, 8, 11 of 21 day schedule Oral dexamethasone 20mg on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 day schedule

Drug: lenalidomide; Drug: Subcutaneous bortezomib; Drug: Dexamethasone

Interventions

lenalidomide DRUG

25mg days 1 - 14 of 21 day schedule

Also known as: Revlimid

RsqVD

Subcutaneous bortezomib DRUG

1.3mg/m2 days 1, 4, 8, 11 of 21 day schedule

Also known as: Velcade

RsqVD

Dexamethasone DRUG

20mg on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 day schedule

Also known as: Decadron

RsqVD

Eligibility Criteria

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

You may qualify if:

• Participants must have a 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 the cases of non-secretory myeloma).
• If no monoclonal protein is detected (non-secretory disease), then ≥ 30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma required.
• 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':
• Hypercalcaemia: serum calcium (corrected for albumin) \> 10.5mg/sL/\>2.65mmol/L or upper limit of normal
• Renal insufficiency defined as serum creatinine \> 2mg/sL/177μmol/L
• Anaemia: Normochromic, normocytic with a haemoglobin value \> 2g/dL below the lower limit of normal or a haemoglobin \< 10g/dL
• Bone lesions (lytic lesions, severe osteopenia or pathologic fractures) as shown by CT scan and/or skeletal survey
• Patient has received no prior treatment with any systemic therapy for the treatment of multiple myeloma.
• Prior treatment of hypercalcaemia 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
• Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible. Two weeks must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and 2 weeks have passed since the last date of therapy.
• Voluntary written informed 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
• Age ≥ 18 years at the time of signing Informed Consent

You may not qualify if:

• Patient has ≥ Grade 2 peripheral neuropathy on clinical examination within 14 days before enrolment
• Renal insufficiency (serum creatinine levels \> 2.5 mg/dL/221μmol/L, calculated creatinine clearance with Cockcroft-Gault formula (see Appendix G) \< 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 haemoglobin \< 8.0 g/dL
• AST (SGOT) and ALT (SGPT) \> 2 x ULN, bilirubin levels 1.5 ULN
• Myocardial infarction within 6 months prior to enrolment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix G), 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)
• Known seropositive for or active HIV infection or active hepatitis B or C viral infection. Patients who are seropositive because of hepatitis B virus vaccine are eligible

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (8)

University Hospital Waterford

Waterford, Co Waterford, Ireland

Location

Cork University Hospital

Cork, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

Mater Misericordiae University Hospital

Dublin, Ireland

Location

St James's Hospital

Dublin, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

University Hospital Limerick

Limerick, Ireland

Location

Midlands Regional Hospital

Tullamore, Ireland

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 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Bortezomib; Dexamethasone; Calcium Dobesilate

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; 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

Study Officials

• Peter O'Gorman, Dr

  Mater Misericordiae University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 11, 2014
• First Posted: August 18, 2014
• Study Start: November 1, 2014
• Primary Completion: October 31, 2019
• Study Completion: April 1, 2020
• Last Updated: July 17, 2020

Record last verified: 2020-07

Locations

IE (8)