Phase II Study of Subcutaneous (SC) Bortezomib, Lenalidomide and Dexamethasone for Relapsed and/or Refractory Multiple Myeloma; Followed by SC Bortezomib Maintenance

NCT01647165 | Withdrawn Phase 2

• 2 other identifiers: 12016912-C-0169
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Bortezomib is a drug approved by the Food and Drug Administration (FDA) to treat patients with multiple myeloma. It is given by intravenous injection. Lenalidomide is a drug that alters the immune system. It may also help suppress tumor growth. It is approved by the FDA to treat some types of blood cancers. Dexamethasone prevents or treats inflammation. It is sometimes used to treat multiple myeloma. Objectives: The purpose of this study examine how the combination of the study drugs affects myeloma. \- Eligibility:

• Participants at least 18 years old who have multiple myeloma that has come back, did not respond to treatment, or worsened while being treated.
• Participants who may be pregnant will be tested to ensure that they are not pregnant. Design:
• Participants will be screened with a history and physical examination. Blood work and urine samples will be taken. A series of x-rays of all bones will be done. A bone marrow biopsy will be done.
• Treatment will be monitored with frequent blood tests and imaging studies.
• Treatment will continue as long as the cancer does not grow or spread and no serious side effects develop.
• There will be up to eight 21-day treatment cycles.
• Bortezomib is given by subcutaneous (under the skin) (SC) injection on days 1, 4, 8, and 11 of the cycle.
• Lenalidomide is given by mouth on days 1 14 of the cycle.
• Dexamethasone is given by mouth on days 1, 2, 4, 5, 8, 9, 11, and 12 of the cycle.
• Following cycle eight, if the disease is stable or better, participants will receive bortezomib SC at the dose given at the end of cycle eight.
• Participants will take valacyclovir or acyclovir while taking bortezomib to prevent virus infections.

Conditions

Multiple Myeloma

Keywords

Maintenance Strategy; Plasma Cell Neoplasm; Proteasome Inhibitor; Immunomodulatory Drugs; Novel Therapy

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  2 years

Secondary Outcomes (2)

• Progression-free survival

  3 years

• Duration of response

  2 years

Interventions

Bortezomib DRUG

Cycle 1-8: 1.0 mg/m2 SC at a concentration of 2.5 mg/ml or 1 mg/ml to the thighs or abdomen on days 1, 4, 8, 11 of a 21 day cycle for 8 cycles.

Lenalidomide DRUG

Cycle 1: 15 mg oral daily on days 2-14 of 21 day cycle; Cycle 2-8: 15 mg oral daily on days 1-14 of a 21 day cycle

Dexamethasone DRUG

Cycle 1: 10 mg oral or IV daily on days 2,4,5,8,9,11,12 of a 21 day cycle; Cycle 2-8: 10 mg oral or IV on days 1, 2, 4, 5, 8, 9, 11, 12 of a 21 day cycle

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed and/or refractory histologically confirmed multiple myeloma as defined by:
• Relapse from complete response with reappearance of the serum or urinary paraprotein, more or equal than 5% bone marrow plasma cells, new lytic bone lesions and /or soft tissue plasmacytomas, an increase in size of residual bone lesions and /or development of hypercalcemia (corrected serum calcium \>11.5 mg/dl) not attributable to another cause.
• Progressive disease: when a complete response has not been achieved, include new or expanding bone lesions, hypercalcemia, and a \>25% increase in serum monoclonal paraprotein concentration, 24-hour urinary light chain excretion, or plasma cells within the bone marrow.
• Refractory disease: Unresponsiveness to current therapy or progressive disease within 60 days of prior treatment.
• Measurable disease within the past 4 weeks defined by any one of the following:
• Serum monoclonal protein greater than or equal to 1.0 g/dL
• Urine monoclonal protein \>200 mg/24 hour
• Serum immunoglobulin free light chain \> 10 mg/dL AND abnormal
• kappa/lambda ratio (reference 0.26-1.65)
• Creatinine Clearance greater than or equal to 60 ml/min. CrCl will be calculated by Cockcroft-Gault method. CrCl (calculated) = (140 Age) times Mass (in kilograms) times \[0.85 if Female\] 72 times Serum Creatinine (in mg/dL). If calculated CrCl based on Cockcroft-Gault method is \< 60 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured CrCl must also be greater than or equal to 60 ml/min for the patient to be eligible.
• Age \> 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of VELCADE, or agree to completely abstain from heterosexual intercourse.
• Absolute neutrophil count (ANC) greater than or requal to 1.0 K/uL, hemoglobin greater than or equal to 8 g/dL (transfusions are permissible), and platelet count greater than or equal to 75K/uL within 7 days before enrollment.
• Adequate hepatic function, with bilirubin \< 1.5 times ULN; AST and ALT \< 3.0 times ULN

You may not qualify if:

• Refractory to lenalidomide and/or bortezomib in the most recent line of therapy
• Prior allogeneic stem cell transplant if the patient has graft versus host disease (GVHD).
• Plasma cell leukemia
• Pregnant or lactating females. Confirmation that the subject is not pregnant must be established by a negative serum \<=-human chorionic gonadotropin (beta hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for postmenopausal or surgically sterilized women.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable.
• Uncontrolled hypertension or diabetes
• Active hepatitis B or C infection
• Patient had 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 must be documented by the investigator as not medically relevant.
• Has refractory GI disease with refractory nausea/vomiting, inflammatory bowel disease, or bowel resection that would prevent absorption
• Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance of study requirements
• Significant neuropathy greater than or equal to Grade 1 with pain or Grade 2 at the time of first dose or within 14 days of enrollment.
• Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
• Active infection requiring treatment within two weeks prior to first dose
• Major surgery within 1 month prior to enrollment
• Hypersensitivity to bortezomib, boron, mannitol or lenalidomide

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Millennium Pharmaceuticals, Inc.: collaborator

Related Publications (3)

• Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004 Oct 28;351(18):1860-73. doi: 10.1056/NEJMra041875. No abstract available.

  PMID: 15509819 BACKGROUND

• Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86. doi: 10.1182/blood-2010-02-268862. Epub 2010 Apr 12.

  PMID: 20385792 BACKGROUND

• San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG; VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008 Aug 28;359(9):906-17. doi: 10.1056/NEJMoa0801479.

  PMID: 18753647 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; Lenalidomide; Dexamethasone

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)

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

Study Officials

• Carl O Landgren, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 19, 2012
• First Posted: July 20, 2012
• Study Start: July 11, 2012
• Primary Completion: June 26, 2015
• Study Completion: June 26, 2015
• Last Updated: December 12, 2019

Record last verified: 2014-03-11