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Multiple Myeloma and Plasma Cell NeoplasmPhase 1NCT00258245

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

A Phase 1 study testing ascorbic acid, arsenic trioxide and bortezomib in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ascorbic acid, arsenic trioxide and bortezomib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
May 2005to Apr 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

Other trials in United States

About this study

Official title: A Phase I Study of Arsenic Trioxide and Ascorbic Acid (ATO/AA) in Combination With Low Dose Velcade-Thalidomide-Dexamethasone (VTD) in Relapsed/Refractory Multiple Myeloma (MM)

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.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the dose-limiting toxicity of arsenic trioxide when given in combination with ascorbic acid, bortezomib, thalidomide, and dexamethasone, particularly in terms of sensory neuropathy, in patients with relapsed or refractory multiple myeloma or plasma cell leukemia.

Secondary

  • Determine the overall response rate, complete response rate, and response duration in patients treated with the maximum tolerated dose of this regimen.
  • Determine whether the addition of arsenic trioxide and ascorbic acid to the treatment regimen (beginning in course 2) increases NFKB inhibition in these patients during courses 2 and 3 compared to course 1.

OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide.

  • Induction therapy: Patients receive bortezomib IV over 3-5 seconds and dexamethasone IV or orally on days 1, 4, 8, and 11 and oral thalidomide once daily on days 1-21 (course 1). For course 2 and all subsequent courses, patients receive arsenic trioxide IV over 1-2 hours, ascorbic acid IV over 15 minutes, bortezomib IV over 3-5 seconds, and dexamethasone IV or orally on days 1, 4, 8, and 11 and thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a plateau in response proceed to maintenance therapy.
  • Maintenance therapy: Patients receive oral dexamethasone every other day and oral thalidomide once daily in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Being tested
ascorbic acid, arsenic trioxide, bortezomib, dexamethasone, thalidomide
Keywords
stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, stage I multiple myeloma
Medical subject headings
Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ascorbic acidDietary supplement

    Also called All Day C CR, Ascot, C Complex, C-500

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

  • arsenic trioxideDrug

    Also called Trisenox®

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

  • bortezomibDrug

    Also called Velcade®

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

  • dexamethasoneDrug

    Also called Dexasone, Decadron, Diodex, Hexadrol

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

  • thalidomideDrug

    Also called Thalomid

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

  • AspirinDrug

    Also called Acuprin 81, Anacin Aspirin Regimen, Ascriptin, Ascriptin Enteric

    Aspirin - 325 mg by mouth (PO) every day

Study groups in NCT00258245
Study groupRoleWhat they receive
Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASAExperimentalBortezomib (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
Receives: Dietary Supplement: ascorbic acid; Drug: arsenic trioxide; Drug: bortezomib; Drug: dexamethasone; Drug: thalidomide; Drug: Aspirin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (2)
  1. 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.

    Measured: at cycle 2 and 6 weeks after

  2. 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.

    Peripheral blood samples are to be obtained at baseline, and 1 hour after the first dose of Bortezomib in cycles 1, 2, and 3 for Pharmacodynamic studies

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2005 (estimated)
  2. Study startMay 2005
  3. Primary completionApr 2008
  4. Study completionApr 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00258245
Sponsor's protocol ID
CDR0000445464
Other IDs
P30CA022453, WSU-D-2869, WSU-HIC-01705M1F
Status last verified
Apr 2013
First submitted
22 Nov 2005
Last updated
29 Apr 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ascorbic acid, arsenic trioxide and bortezomib in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Days 1, 4, 8 & 11 of each 21 day cycle). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2013.

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