Lenalidomide/Bortezomib/Dexamethasone & CNTO 328 in Transplant Eligible Newly Diagnosed Multiple Myeloma (MM)

NCT01531998 | Completed Phase 1 Results

• 2 other identifiers: 2010-0073NCI-2012-00218
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of Siltuximab that can be given in combination with Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone to patients with MM. The safety of this drug combination will also be studied.

Conditions

Myeloma

Keywords

Myeloma; Multiple Myeloma; MM; Newly diagnosed; Lenalidomide; CC-5013; Revlimid; Bortezomib; Velcade; LDP-341; MLN341; PS-341; Siltuximab; CNTO 328; Anti-IL-6 Antibody; Dexamethasone; Decadron; M. D. Anderson Symptom Inventory Module; MDASI-MM; Questionnaires; Surveys

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Siltuximab

  Maximum tolerated dose (MTD) defined as follows: At first dose level, if greater than 1 out of 3 patients or greater than 1 out of 6 patients experience dose limiting toxicity (DLT), the dose level exceeds the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) defined as toxicities graded in severity according to the guidelines outlined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

  21 days

Secondary Outcomes (1)

• Number of Participants With Response

  Evaluated after eight cycles of 21 days.

Study Arms (1)

Siltuximab + Bortezomib + Lenalidomide

EXPERIMENTAL

Induction: Lenalidomide 25 mg orally Days 1-14; Bortezomib 1.3 mg/m2 intravenous Days 1, 4, 8 and 11; Dexamethasone 20 mg orally Days 1, 2, 4, 5, 8, 9, 11, 12. Siltuximab 11 mg/kg intravenous Day 1. If delayed transplant, induction therapy continued up to 2 cycles beyond achieving a CR/nCR (minimum of 4 cycles of therapy and a maximum of 8 cycles of therapy) and then transition to maintenance regimen described below. Maintenance therapy: Lenalidomide at last tolerated dose Day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg. Siltuximab 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. Bortezomib at last tolerated dose Day 1 and Day 8 Dexamethasone at last tolerated dose or 20 mg weekly.

Drug: Lenalidomide; Drug: Bortezomib; Drug: Siltuximab; Drug: Dexamethasone; Behavioral: Questionnaires

Interventions

Lenalidomide DRUG

Induction Phase: 25 mg by mouth daily on Days 1-14. Maintenance Phase: at last tolerated dose from Induction Phase day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg.

Also known as: CC-5013, Revlimid

Siltuximab + Bortezomib + Lenalidomide

Bortezomib DRUG

Induction Phase: 1.3 mg/m2 by vein daily on Days 1, 4, 8 and 11. Maintenance Phase: 1.3 mg/m2 by vein or last tolerated dose on Day 1 and Day 8.

Also known as: Velcade, LDP-341, MLN341, PS-341

Siltuximab + Bortezomib + Lenalidomide

Siltuximab DRUG

Induction Phase Starting Dose: 11 mg/kg by vein on Day 1. Maintenance Phase: 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy.

Also known as: CNTO 328, Anti-IL-6 Antibody

Siltuximab + Bortezomib + Lenalidomide

Dexamethasone DRUG

Induction Phase: 20 mg by mouth on Days 1, 2, 4, 5, 8, 9, 11, 12. Maintenance Phase: 20 mg by mouth on Days 1, 2, 4, 5, 8, 9, 11, 12. If participant still on Dexamethasone, when entering Maintenance Phase, dose reduced to 20 mg a week.

Also known as: Decadron

Siltuximab + Bortezomib + Lenalidomide

Questionnaires BEHAVIORAL

M. D. Anderson Symptom Inventory Module (MDASI-MM) completed Day 1, Day 8 of Cycle 1 - 8, and on Day 1 of Cycle 9 and beyond.

Also known as: Surveys

Siltuximab + Bortezomib + Lenalidomide

Eligibility Criteria

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

You may qualify if:

• \. Multiple Myeloma Diagnosis: Subject was previously diagnosed with multiple myeloma by the International Myeloma Foundation 2003 Diagnostic Criteria: IMF Diagnostic Criteria: DIAGNOSTIC CRITERIA: ALL 3 REQUIRED 1. Monoclonal plasma cells in the bone marrow \> 10% and/or presence of a biopsy-proven plasmacytoma 2. Monoclonal protein present in the serum and/or urine \* 3. Myeloma-related organ dysfunction (1 or more) \*\* ; \[C\] Calcium elevation in the blood S. Calcium \>10.5 mg/l or upper limit of normal ; \[R\] Renal insufficiency ; \[A\] Anemia Hemoglobin \< 10 g/dl or 2 g \< normal ; \[B\] Lytic bone lesions or osteoporosis \*\*\*
• Patient must not have been previously treated with any prior 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
• Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible. One week must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have start of the protocol therapy (Cycle 1 Day 1) deferred until the radiotherapy is completed and one week 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.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International unit (mIU)/mL 10 - 14 days prior to therapy and repeated again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
• Age \>/= 18 years at the time of signing Informed Consent.
• All necessary baseline studies for determining eligibility must be obtained within 28 days prior to enrollment.
• Subject has a Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist.
• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
• Subject must be able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• Patient has \>/=Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment.
• Renal insufficiency (Creatinine Clearance \<30 mL/min by Cockcroft -Gault formula).
• Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count \>/= 50,000 cells/mm\^3).
• Subjects with an absolute neutrophil count (ANC) \< 1000 cells/mm\^3. Growth factors may not be used to meet ANC eligibility criteria.
• Total bilirubin \> 1.5 mg/dL
• Subjects with a hemoglobin \< 8.0 g/dL (Transfusion are permitted).
• AST (SGOT and ALT (SGPT) \>/= 2 x upper limit of normal (ULN)
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Clinically relevant active infection requiring intravenous antibiotics
• Serious co-morbid medical conditions such as uncontrolled chronic obstructive or chronic restrictive pulmonary disease, and cirrhosis.
• Any 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 medical or psychiatric illness likely to interfere with participation in this clinical study.
• Uncontrolled diabetes mellitus (Fasting Blood Sugar \> 400 mg/dl despite medical treatment)
• Hypersensitivity to acyclovir or similar anti-viral drug

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Janssen Services, LLC: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Multiple Myeloma

Interventions

Lenalidomide; Bortezomib; siltuximab; Dexamethasone; Calcium Dobesilate; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

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; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Jatin J. Shah, MD/Associate Professor, Lymphoma/Myeloma
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-2860

Study Officials

• Jatin J. Shah, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2012
• First Posted: February 13, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 19, 2015
• Results First Posted: June 19, 2015

Record last verified: 2015-06

Locations

US (1)