Treatment Optimization in Patients With Untreated Multiple Myeloma

NCT02145598 | Terminated Phase 2

• 2 other identifiers: GERMAIN2012-003023-38
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 19

Brief Summary

This is a multicenter, randomized, blinded, 2-arm phase IIb trial that will compare the efficacy and safety of Lenalidomide maintenance after Bortezomib/Melphalan/Prednison (VMP) induction to VMP without maintenance (Placebo). In addition the trial will assess the treatment of Revlimid/low dose Dexamethasone (Rd) as Salvage after VMP without sufficient response (less than PR) in an observational arm. Key eligibility criteria include patients with newly diagnosed multiple myeloma and who are 65 years of age or older or are not candidates for high-dose chemotherapy and autologous stem cell transplantation. Patients with poor performance status or serious coexistent medical conditions will be excluded from this study. After registration all patients receive 6 cycles VMP (modified according to Mateos et al.). Patients who receive at least a PR and completed VMP can be randomized to either Lenalidomide 10 mg/d continuously maintenance or to placebo. Randomization will be stratified according to the quality of response after VMP induction (PR vs. VGPR + stringent complete remission \[sCR\] + CR). Patients that are not able to complete VMP due to toxicity but reached at least a PR after a minimum of four cycles of therapy should immediately proceed to randomization. Blinded phase continues until progression or end of study. After unblinding, patients who received placebo should be treated with Rd. Patients that do not reach PR after induction with VMP or are progressive during treatment with VMP should not be randomized, but switched to the observation arm and treated with Rd immediately. The study treatment ends with the confirmed progression on maintenance treatment (Lenalidomide or placebo) for patients that reached PR with induction treatment, or with the confirmed progression on second-line therapy with Revlimid® and Dexamethasone for patients that did not reach PR on induction treatment. All patients will be followed up every 3 months after end of study treatment, until end of study. The study ends two years after Last Patient In (i.e. randomization for maintenance) if sufficient events for the primary endpoint were received, but not later than 8 years after trial initiation (whatever comes first).

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Revlimid; Lenalidomide maintenance

Outcome Measures

Primary Outcomes (1)

• Median Progression free survival

  time from randomization to the first documentation of disease progression or death due to any cause, whichever comes first, assessed up to the end of the study (maximum of 8 years)

  maximum of 8 years

Secondary Outcomes (7)

• overall survival

  5 years after randomization

• sequence progression-free survival

  maximum of 8 years

• efficacy parameters according to the international uniform response criteria

  after VMP (31 weeks) and 6 months of maintenance or placebo

• number and indication of adverse events

  maximum of 8 years

• Quality of life

  maximum of 8 years

Study Arms (2)

Lenalidomide

EXPERIMENTAL

Lenalidomide 10mg/day

Drug: Lenalidomide

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Lenalidomide DRUG

after 6 cycles VMP Patients will receive Lenalidomide given as two capsules 5 mg capsules p.o. daily until progressive disease (PD)

Also known as: Revlimid

Lenalidomide

Placebo DRUG

after 6 cycles VMP Patients will receive Placebo given as two capsules 5 mg capsules p.o. daily until progressive disease (PD)

Placebo

Eligibility Criteria

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

You may qualify if:

• Must understand and voluntarily sign an informed consent form.
• Must be ≥18 years of age at the time of signing the informed consent form.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:
• Multiple Myeloma (MM) diagnostic criteria (all 3 required):
• Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy-proven plasmacytoma
• Monoclonal protein present in the serum and/or urine
• Myeloma-related organ dysfunction (at least one of the following):
• \[C\] Calcium elevation in the blood (serum calcium \>10.5 mg/dl or upper limit of normal)
• \[R\] Renal insufficiency (serum creatinine \>2 mg/dl)
• \[A\] Anemia (hemoglobin \<10 g/dl or 2 g \< laboratory normal)
• \[B\] Lytic bone lesions or osteoporosis
• AND have measurable disease by protein electrophoresis analyses as defined by the following:
• Immunoglobulin (Ig)G multiple myeloma: Serum monoclonal paraprotein (M-protein) level
• g/dl or urine M-protein level - 200 mg/24 hours

You may not qualify if:

• Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid \[i.e., less than or equal to the equivalent of Dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of registration\]).
• Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, patient with unstable cardiac disease as defined by: Cardiac events such as MI within the past 6 months, NYHA (New York Heart Association) heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; patients with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
• Pregnant or breast feeding females.
• Any of the following laboratory abnormalities within 1 week prior to registration:
• Absolute neutrophil count (ANC) \< 1,000/µL (1.0 x 109/L) without the use of colony stimulating factors within 14 days before the laboratory test. Untransfused platelet count \< 50,000 cells/µL (50 x 109/L)
• Hemoglobin \< 7.5 g/dL (4.6 mmol/L) (regardless of transfusion support or prior medication with erythropoietin)
• Serum sGOT/AST (serum glutamic-oxaloacetic transaminase/ aspartate aminotransferase) or SGPT(serum glutamate pyruvate transaminase)/ALT \> 3.0 x upper limit of normal (ULN)
• Corrected serum calcium \> 14 mg/dL (\> 3.5 mmol/L)
• Renal failure with creatinine clearance (CLCR)\< 15 ml/min or requiring hemodialysis or peritoneal dialysis.
• Psychiatric illness that would prevent the subject from signing the informed consent form or from completion of treatment according to the protocol.
• Patient currently is enrolled in another clinical research study or has been enrolled in such a study within 4 weeks before randomization/registration and/or is receiving an investigational agent for any reason or has received such an agent within 4 weeks before registration.
• Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for 3 years. Exceptions include the following, if treated with curative intent:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix

Sponsors & Collaborators

• Dr. med. Lars-Olof Muegge: lead

Study Sites (19)

Charité - Campus Benjamin Franklin Medizinische Klinik II

Berlin, 12203, Germany

Location

Städtisches Klinikum Brandenburg

Brandenburg, 14770, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

Gemeinschaftspraxis Mohm / Prange-Krex

Dresden, 01307, Germany

Location

Onkologische Schwerpunktpraxis

Dresden, 01307, Germany

Location

Internistische Gemeinschaftspraxis

Güstrow, 18273, Germany

Location

Universitätsklinkum Halle

Halle, 06120, Germany

Location

Universitätsklinikum Jena, Klinik für Innere Medizin II, Abt. Hämatologie und internistische Onkologie

Jena, 07740, Germany

Location

Universitätsklinikum Leipzig, Department für Innere Medizin

Leipzig, 04103, Germany

Location

Dr. Aldaoud - Dr. Schwarzer Forschungsgesellschaft mbH

Leipzig, 04289, Germany

Location

Gemeinschaftspraxis Uhle, Müller, Kröning, Jentsch-Ullrich

Magdeburg, 39104, Germany

Location

Universitätsklinikum Magdeburg AöR

Magdeburg, 39120, Germany

Location

Klinikum Magdeburg gGmbH

Magdeburg, 39130, Germany

Location

Universitätsmedizin Rostock

Rostock, 18057, Germany

Location

Klinikum Südstadt Rostock

Rostock, 18059, Germany

Location

Johanniter-Krankenhaus Gethin-Stendal GmbH

Stendal, 39576, Germany

Location

Medizinisches Versorgungszentrum GmbH

Weiden, 92637, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Heinrich-Breun-Klinikum gGmbH

Zwickau, 08060, Germany

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

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)

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

Study Officials

• Annamaria Brioli, MD

  Jena University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 13, 2013
• First Posted: May 23, 2014
• Study Start: August 1, 2013
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2018
• Last Updated: January 16, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (19)