S0833, Bortezomib, Thalidomide, Lenalidomide, Combination Chemotherapy, and Autologous Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma

NCT01055301 | Withdrawn Phase 2 DMC

• 2 other identifiers: S0833U10CA032102
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 21

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as thalidomide and lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, cisplatin, doxorubicin hydrochloride, cyclophosphamide, etoposide, and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Combining chemotherapy with autologous stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Giving bortezomib, thalidomide, and combination chemotherapy before and after transplant and lenalidomide after transplant may be an effective treatment for multiple myeloma. PURPOSE: This phase II trial is studying how well giving bortezomib, thalidomide, and lenalidomide together with combination chemotherapy and autologous stem cell transplant works in treating patients with newly diagnosed multiple myeloma.

Conditions

Multiple Myeloma; Plasma Cell Myeloma

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 3 years

  3 years

Secondary Outcomes (3)

• Overall survival

  3 years

• Frequency and severity of toxicities

  3 years

• Gene expression profiling analysis of CD138+ purified plasma cells

  3 years

Study Arms (1)

treatment

EXPERIMENTAL

Ind (1cycle): bort 1mg/m2 IV/SQ D1,4,8,11 D1-4: thalid 200mg/d \& dex 20mg/d PO; cisplatin \& dox 10mg/m2/d, cyclophos 400mg/m2/d, etoposide 40mg/m2/d contIV; enoxaparin 40mg/d SQ prn. PBSC Coll: at recovery per local standard Bridging (before/between trans/after Cons): thal 50mg/d D1-21 \& dex 20mg D1,8,15 PO Tandem Trans (x2): bort 1mg/m2 IV/SQ D-4,-1 D-4to-1: mel 50 mg/m2 IV, thal 200mg/d \& dex 40mg/d PO PBSC \>/=200x10\^6 cells Cons (1cycle): same as Ind except cis/dox 7.5mg/m2/d, cyclo 300mg/m2/d, no enox Maint(\</= 3 yrs): D1,8,15,22:bort 1mg/m2 IV/SQ, dex 20mg/d PO; len 20mg/d PO D1-20

Drug: bortezomib; Drug: cisplatin; Drug: cyclophosphamide; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: lenalidomide; Drug: melphalan; Drug: thalidomide; Genetic: gene expression analysis; Genetic: microarray analysis; Other: laboratory biomarker analysis; Procedure: autologous-autologous tandem hematopoietic stem cell transplantation

Interventions

bortezomib DRUG

Also known as: bort

treatment

cisplatin DRUG

treatment

cyclophosphamide DRUG

treatment

dexamethasone DRUG

treatment

doxorubicin hydrochloride DRUG

treatment

etoposide DRUG

treatment

lenalidomide DRUG

treatment

melphalan DRUG

treatment

thalidomide DRUG

treatment

gene expression analysis GENETIC

treatment

microarray analysis GENETIC

treatment

laboratory biomarker analysis OTHER

treatment

autologous-autologous tandem hematopoietic stem cell transplantation PROCEDURE

treatment

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Newly diagnosed active multiple myeloma (MM) * Measurable disease * Non-secretory disease allowed provided patient has ≥ 20% plasmacytosis or multiple (\> 3) focal plasmacytomas on skeletal survey and/or MRI PATIENT CHARACTERISTICS: * Zubrod performance status (PS) 0-2 (Zubrod PS 3-4 allowed if based solely on bone pain) * ANC ≥ 1,500/mm\^3\* * Platelet count ≥ 150,000/mm\^3\* * Serum creatinine clearance of ≥ 60 mL/min * Patients with creatinine clearance of \< 60 mL/min receive a lower dose of melphalan * No patients receiving or planning to receive dialysis * Total bilirubin ≤ 1.5 times upper limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Must be fully aware of the teratogenic potential of thalidomide * Must be willing to comply with the FDA-mandated S.T.E.P.S. program * Ejection fraction \> 40% as measured by MUGA scan or two-dimensional ECHO * No peripheral neuropathy ≥ grade 2 per CTCAE v. 4.0 * No known hypersensitivity to bortezomib, boron, or mannitol * No uncontrolled diabetes defined as fasting glucose level \> 200 mg/dL on at least more than two occasions or more that two serum random blood levels \> 300 mg/dL despite adequate treatment * Patients with a history of diabetes mellitus requiring treatment should be on a stable regimen and have their blood glucose closely monitored * No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment within the past year NOTE: \*Unless myeloma-related marrow infiltration is documented, defined as ≥ 30% marrow cellularity with 50% of the cells being malignant plasma cells. PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior chemotherapy or radiotherapy * No more than 1 prior course of chemotherapy for MM * Prior chemotherapy must not have included melphalan * No prior radiotherapy to large area of the pelvis (more than half of the pelvis) * Prior radiotherapy for symptomatic localized bone lesions or impending cord compression allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

Study Sites (21)

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, 71315-3198, United States

Location

Hematology-Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

University of Mississippi Cancer Clinic

Jackson, Mississippi, 39216, United States

Location

Island Hospital Cancer Care Center at Island Hospital

Anacortes, Washington, 98221, United States

Location

St. Joseph Cancer Center

Bellingham, Washington, 98225, United States

Location

Olympic Hematology and Oncology

Bremerton, Washington, 98310, United States

Location

Highline Medical Center Cancer Center

Burien, Washington, 98166, United States

Location

Columbia Basin Hematology

Kennewick, Washington, 99336, United States

Location

Skagit Valley Hospital Cancer Care Center

Mount Vernon, Washington, 98274, United States

Location

Harrison Poulsbo Hematology and Onocology

Poulsbo, Washington, 98370, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Minor and James Medical, PLLC

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Group Health Central Hospital

Seattle, Washington, 98112, United States

Location

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, 98122-4307, United States

Location

University Cancer Center at University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

North Puget Oncology at United General Hospital

Sedro-Woolley, Washington, 98284, United States

Location

Cancer Care Northwest - Spokane South

Spokane, Washington, 99202, United States

Location

Evergreen Hematology and Oncology, PS

Spokane, Washington, 99218, United States

Location

Wenatchee Valley Medical Center

Wenatchee, Washington, 98801-2028, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Etoposide; Lenalidomide; Melphalan; Thalidomide; Gene Expression Profiling; Microarray Analysis

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Genetic Techniques; Investigative Techniques; Microchip Analytical Procedures

Study Officials

• Muneer H. Abidi, MD

  Barbara Ann Karmanos Cancer Institute

  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: January 22, 2010
• First Posted: January 25, 2010
• Study Start: July 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: March 6, 2015

Record last verified: 2015-03

Locations

US (21)