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.
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
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- 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
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 group | Role | What they receive |
|---|---|---|
| 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 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.
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)
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
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.
- First posted24 Nov 2005 (estimated)
- Study startMay 2005
- Primary completionApr 2008
- Study completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Barbara Ann Karmanos Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jeffrey A. Zonder, MD, Study chair, Barbara Ann Karmanos Cancer Institute
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
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00258245
- Acronym / sponsor ID
- CDR0000445464
- Keywords
- stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, stage I multiple myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2005
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 24 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA | Experimental | Dietary Supplement: ascorbic acid, Drug: arsenic trioxide, Drug: bortezomib, Drug: dexamethasone, Drug: thalidomide, Drug: AspirinBortezomib (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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ascorbic acidAlso: All Day C CR, Ascot, C Complex, C-500Ascorbic Acid (Vit C)- 1000 mg IVPB after Arsenic Trioxide [ATO] days 1, 4, 8, 11 | Dietary supplement | Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA |
| arsenic trioxideAlso: Trisenox®Arsenic Trioxide (Trisenox)- 0.10→0.15→0.25 mg/kg/dose IVPB days 1, 4, 8, 11 | Drug | Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA |
| bortezomibAlso: Velcade®Bortezomib (Velcade)- 0.7→1.0 mg/m2 IVP days 1, 4, 8, 11 | Drug | Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA |
| dexamethasoneAlso: Dexasone, Decadron, Diodex, HexadrolDexamethasone (Decadron)- 40 mg/days IVPB or PO d 1, 4, 8, 11 | Drug | Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA |
| thalidomideAlso: ThalomidThalidomide (Thalomid) - 50 mg/day by mouth (PO) | Drug | Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA |
| AspirinAlso: Acuprin 81, Anacin Aspirin Regimen, Ascriptin, Ascriptin EntericAspirin - 325 mg by mouth (PO) every day | Drug | Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA |
Primary outcome
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
2 secondary outcomes
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.
Time frame: 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.
Time frame: At baseline and 1 hour after the first dose of Bortezomib in cycles 1, 2, and 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey A. Zonder, MD study chair
Barbara Ann Karmanos Cancer Institute
1 site in 1 country: see every site and its status.
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.