Arsenic Trioxide and Ascorbic Acid Combined With Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma or Plasma Cell Leukemia

NCT00258245 | Completed Phase 1 DMC

• 4 other identifiers: CDR0000445464P30CA022453WSU-D-2869WSU-HIC-01705M1F
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Ascorbic acid may help arsenic trioxide work better by making cancer cells more sensitive to the drug. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Giving arsenic trioxide and ascorbic acid together with bortezomib, thalidomide, and dexamethasone may stop the growth of and kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with ascorbic acid, bortezomib, thalidomide, and dexamethasone in treating patients with relapsed or refractory multiple myeloma or plasma cell leukemia.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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

Outcome Measures

Primary Outcomes (1)

• To determine if arsenic trioxide and ascorbic acid at doses up to 0.25 mg/mg/dose can be given in combination with reduced-dose dexamethasone, bortezomib and thalidomide without dose limiting toxicity, especially sensory neuropathies.

  Days 1, 4, 8 & 11 of each 21 day cycle

Secondary Outcomes (2)

• Estimate the Overall Response Rate (ORR), Complete Response Rate (CRR), and Response Duration (RD) in patients treated with the Maximally Tolerated Dose (MTD) of this regimen.

  at cycle 2 and 6 weeks after

• Determine if addition of Arsenic Trioxide[AT]/Ascorbic Acid (Vit C)[AA] starting in cycle 2 of treatment increases NF-kappa-B [NFKB] inhibition in cycles 2 and 3 compared to cycle 1.

  At baseline and 1 hour after the first dose of Bortezomib in cycles 1, 2, and 3

Study Arms (1)

Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA

EXPERIMENTAL

Bortezomib (Velcade)- 0.7→1.0 mg/m2 IVP d 1, 4, 8, 11; Arsenic Trioxide \[AT\] (Trisenox)- 0.10→0.15→0.25 mg/kg/dose IVPB days 1, 4, 8, 11; Thalidomide (Thalomid)- 50 mg/day by mouth (PO); Dexamethasone (Decadron)- 40 mg/d IVPB or by mouth (PO) d 1, 4, 8, 11; Ascorbic Acid (Vit C)- 1000 mg IVPB p Arsenic Trioxide (ATO) days 1, 4, 8, 11; Aspirin (ASA)- 325 mg by mouth (PO) every day

Dietary Supplement: ascorbic acid; Drug: arsenic trioxide; Drug: bortezomib; Drug: dexamethasone; Drug: thalidomide; Drug: Aspirin

Interventions

ascorbic acid DIETARY_SUPPLEMENT

Ascorbic Acid (Vit C)- 1000 mg IVPB after Arsenic Trioxide \[ATO\] days 1, 4, 8, 11

Also known as: All Day C CR, Ascot, C Complex, C-500, C-500-Gr, C-Time, Cecon, Cemill 1000, Cemill 500, Centrum Singles-Vitamin C, Cevi-Bid, N Ice with Vitamin C, Special C, Sunkist Vitamin C, Vicks Vitamin C Drops, Vitamin C TR

Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA

arsenic trioxide DRUG

Arsenic Trioxide (Trisenox)- 0.10→0.15→0.25 mg/kg/dose IVPB days 1, 4, 8, 11

Also known as: Trisenox®

Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA

bortezomib DRUG

Bortezomib (Velcade)- 0.7→1.0 mg/m2 IVP days 1, 4, 8, 11

Also known as: Velcade®

Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA

dexamethasone DRUG

Dexamethasone (Decadron)- 40 mg/days IVPB or PO d 1, 4, 8, 11

Also known as: Dexasone, Decadron, Diodex, Hexadrol, Maxidex, Dexamethasone Sodium Phosphate, Dexamethasone Acetate

Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA

thalidomide DRUG

Thalidomide (Thalomid) - 50 mg/day by mouth (PO)

Also known as: Thalomid

Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA

Aspirin DRUG

Aspirin - 325 mg by mouth (PO) every day

Also known as: Acuprin 81, Anacin Aspirin Regimen, Ascriptin, Ascriptin Enteric, Aspergum, Aspidrox, Aspir-Low, Aspir-Mox, Aspir-trin, Aspirtab, Bayer Aspirin, Bufferin, Buffex, Easprin, Ecotrin, Ecpirin, Empirin, Entaprin, Entercote, Fasprin, Genacote, Gennin-FC, Genprin, Halfprin, Magnaprin, Med Aspirin, Migralex, Miniprin, Minitabs, Norwich Aspirin, Ridiprin, Sloprin, St. Joseph Aspirin, Uni-Buff, Uni-Tren, Valomag, Zero-Order Release, Zorprin

Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed multiple myeloma (MM) or plasma cell leukemia meeting 1 of the following criteria: * Relapsed or refractory disease after treatment with prior effective therapy * Exhibited \< a partial response to the last therapy * Measurable disease, defined by 1 of the following: * Serum M protein ≥ 1.0 g/dL * Urine M-protein ≥ 500 mg/24 hours * Plasmacytoma with bidimensional measurements on CT scan or MRI (each axis ≥ 1 cm) * Previously treated with ≥ 1 induction chemotherapy regimen for MM * No known CNS involvement by multiple myeloma PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod or SWOG 0-2 OR * Karnofsky 60-100% Life expectancy * More than 12 weeks Hematopoietic * WBC ≥ 1,500/mm\^3 * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 80,000/mm\^3 * Hemoglobin ≥ 8.5 g/dL * No history of heparin-induced thrombocytopenia * Low blood counts allowed if marrow is heavily infiltrated by multiple myeloma Hepatic * Bilirubin ≤ 1.5 times upper limit normal (ULN) * AST and ALT ≤ 2.5 times ULN Renal * Creatinine ≤ 2.5 mg/dL Cardiovascular * QTc \< 480 msec on EKG in the presence of serum potassium ≥ 4.0 mEq/dL and serum magnesium ≥ 1.8 mg/dL * LVEF ≥ 55% by ECHO or MUGA * No prior deep vein thrombosis, unless on concurrent anticoagulation * No symptomatic congestive heart failure * No unstable angina pectoris * No history of ventricular arrhythmia Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after completion of study treatment * No history of allergic reactions or severe adverse reactions attributed to compounds of similar chemical or biological composition to study drugs * No other malignancy in the past 2 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix * No peripheral neuropathy ≥ grade 2 * No ongoing or active infection requiring IV antibiotics * No psychiatric illness or social situation that would preclude study compliance * No other uncontrolled illness * Controlled HIV disease allowed as long as there are no associated comorbid complications * No active peptic ulcer disease * No other condition that would confer a high risk of bleeding complications PRIOR CONCURRENT THERAPY: Biologic therapy * More than 4 weeks since prior thalidomide or lenalidomide for MM * Prior autologous or allogeneic stem cell transplant for MM allowed * Concurrent hematopoietic growth factors (e.g., epoetin alfa, filgrastim \[G-CSF\]) for MM allowed Chemotherapy * See Disease Characteristics * More than 4 weeks since prior arsenic trioxide for MM Endocrine therapy * More than 4 weeks since prior corticosteroids for MM Radiotherapy * More than 4 weeks since prior therapeutic radiotherapy (e.g., to plasmacytomas) * Palliative radiotherapy for painful symptomatic lytic skeletal lesions allowed within the past 4 weeks Surgery * Not specified Other * More than 4 weeks since prior cytotoxic agents or other therapy (e.g., bortezomib) for MM * More than 30 days (or 5 half-lives) since prior investigational agents * Concurrent bisphosphonates for MM allowed * No other concurrent anticancer therapy * No other concurrent investigational agents

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

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Ascorbic Acid; Arsenic Trioxide; Bortezomib; Dexamethasone; Calcium Dobesilate; dexamethasone 21-phosphate; dexamethasone acetate; Thalidomide; Aspirin; aspirin, aluminum hydroxide, magnesium hydroxide drug combination

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)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols

Study Officials

• Jeffrey A. Zonder, MD

  Barbara Ann Karmanos Cancer Institute

  STUDY CHAIR

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: November 22, 2005
• First Posted: November 24, 2005
• Study Start: May 1, 2005
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: April 29, 2013

Record last verified: 2013-04

Locations

US (1)