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

This study has been completed.
Sponsor:
Collaborator:
Janssen Services, LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01531998
First received: February 9, 2012
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Myeloma
Drug: Lenalidomide
Drug: Bortezomib
Drug: Siltuximab
Drug: Dexamethasone
Behavioral: Questionnaires
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Single-Arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment With Lenalidomide, Bortezomib, Dexamethasone and Siltuximab (CNTO 328) in Subjects With Newly Diagnosed, Previously Untreated Multiple Myeloma Requiring Systemic Chemotherapy

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Siltuximab [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Response Rate [ Time Frame: Evaluated after eight 21 day cycles. ] [ Designated as safety issue: No ]
    Overall response rate defined as (stringent) complete remission (CR)/near complete remission (nCR)/very good partial remission (VGPR)/partial remission (PR) after 8 cycles.


Enrollment: 14
Study Start Date: May 2012
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Siltuximab + Bortezomib + Lenalidomide

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
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.
Other Names:
  • CC-5013
  • Revlimid
Drug: Bortezomib

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.

Other Names:
  • Velcade
  • LDP-341
  • MLN341
  • PS-341
Drug: Siltuximab

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.

Other Names:
  • CNTO 328
  • Anti-IL-6 Antibody
Drug: Dexamethasone

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.

Other Name: Decadron
Behavioral: Questionnaires
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.
Other Name: Surveys

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 1. 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 ***
  2. Continuation from Inclusion # 1: *If no monoclonal protein is detected (non-secretory disease), then > 30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma required ** A variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification of myeloma if proven to be myeloma related. *** If a solitary (biopsy-proven) plasmacytoma or osteoporosis alone (without fractures) are the sole defining criteria, then > 30% plasma cells are required in the bone marrow.
  3. 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
  4. 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.
  5. 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.
  6. 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.
  7. Age >/= 18 years at the time of signing Informed Consent.
  8. All necessary baseline studies for determining eligibility must be obtained within 28 days prior to enrollment.
  9. Subject has a Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  10. All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist.
  11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
  12. Subject must be able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

  1. Patient has >/=Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment.
  2. Renal insufficiency (Creatinine Clearance <30 mL/min by Cockcroft -Gault formula).
  3. 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).
  4. Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm^3. Growth factors may not be used to meet ANC eligibility criteria.
  5. Total bilirubin > 1.5 mg/dL
  6. Subjects with a hemoglobin < 8.0 g/dL (Transfusion are permitted).
  7. AST (SGOT and ALT (SGPT) >/= 2 x upper limit of normal (ULN)
  8. 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.
  9. Clinically relevant active infection requiring intravenous antibiotics
  10. Serious co-morbid medical conditions such as uncontrolled chronic obstructive or chronic restrictive pulmonary disease, and cirrhosis.
  11. 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.
  12. Female subject is pregnant or breast-feeding.
  13. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  14. Uncontrolled diabetes mellitus (Fasting Blood Sugar > 400 mg/dl despite medical treatment)
  15. Hypersensitivity to acyclovir or similar anti-viral drug
  16. Known history of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).
  17. Patients with known history of HIV, Hep B and C.
  18. Hypersensitivity to boron or mannitol, or compounds containing these components
  19. Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01531998

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Janssen Services, LLC
Investigators
Principal Investigator: Jatin J. Shah, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01531998     History of Changes
Other Study ID Numbers: 2010-0073, NCI-2012-00218
Study First Received: February 9, 2012
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Lenalidomide
Thalidomide
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014