Multiple Myeloma and Plasma Cell NeoplasmPhase 1/2NCT00006021
Arsenic Trioxide Plus Vitamin C in Treating Patients With Recurrent or Refractory Multiple Myeloma
A Phase 1/2 study testing ascorbic acid and arsenic trioxide in people with Multiple Myeloma and Plasma Cell Neoplasm, run by University of Miami at 4 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vitamin C may increase the effectiveness of arsenic trioxide by making cancer cells more sensitive to the drug. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- ascorbic acid and arsenic trioxide
- How many people
- 22 participants
- Where
- 4 sitesUnited States
- Study dates
- Jun 2000to Mar 2007
- Phase
- Phase 1/2
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed multiple myeloma
- M-protein by serum protein electrophoresis or urine protein electrophoresis
- Quantitative determination of immunoglobulin
- Bone marrow biopsy and aspirate with a plasma cell count greater than 10%
- Refractory or chemoresistant disease defined as failure to respond (less than 50% reduction in M protein level) or progression within 2 months after receiving at least 2 chemotherapy regimens including:
- Alkylating based regimen (melphalan) in combination with steroids (prednisone) or other chemotherapy regimens (e.g., vincristine, bleomycin, melphalan, cyclophosphamide, and prednisone or vincristine, carmustine, doxorubicin, and prednisone)
- Vincristine, doxorubicin, and dexamethasone (VAD) regimen
- Pulse therapy with high dose steroids alone
- High dose alkylating agent and autologous stem cell transplantation
- Allogeneic bone marrow transplantation
- Plateau phase defined as M protein in the serum or urine for more than 6 weeks despite response to prior therapy
- Must have received at least 2 of the chemotherapy regimens listed above or equivalent regimens
- Recurrent disease defined as progression more than 2 months after initial therapy and failure to respond (less than 50% reduction or progression in M protein levels) to 1 chemotherapy regimen listed above or other salvage regimens (e.g., high-dose cyclophosphamide or topotecan)
- Must have received VAD or other equivalent chemotherapy regimen
- Should be considered for autologous or allogenic transplantation
- Prior local radiotherapy allowed
PATIENT CHARACTERISTICS:
Age:
- Over 18
Performance status:
- Karnofsky 60-100%
Life expectancy:
- Not specified
Hematopoietic:
- WBC at least 2,000/mm^3*
- Platelet count at least 50,000/mm^3* NOTE: *Unless attributable to bone marrow infiltration by multiple myeloma
Hepatic:
- Bilirubin less than 3 mg/dL
- Transaminases less than 2.5 times upper limit of normal (ULN)
Renal:
- Creatinine less than 1.5 times ULN OR
- Creatinine clearance at least 60 mL/min
Cardiovascular:
- No cardiac arrhythmias including recurrent supraventricular arrhythmia, any type of sustained ventricular arrhythmia, or conduction block (atrioventricular block grade II or III, left bundle branch block)
- Ejection fraction at least 30%
- No uncontrolled ischemic heart disease
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 4 months after study
- HIV negative
- No grade 3 or higher neurological disorder, including seizure disorders
- No underlying medical condition that would preclude study
- No other active malignancy except adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
Chemotherapy:
- See Disease Characteristics
- At least 2 weeks since prior chemotherapy
Endocrine therapy:
- See Disease Characteristics
- Concurrent steroid treatment allowed except for primary treatment of myeloma
Radiotherapy:
- See Disease Characteristics
- Concurrent local radiotherapy for pain or symptom control allowed provided the pain or symptom is not related to disease progression
Surgery:
- Not specified
Other:
- No other concurrent ascorbic acid supplements
- No other concurrent investigational drug or therapy
- Concurrent bisphosphonates allowed
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Cedars Medical Center
Miami, Florida, 33136
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Baptist-South Miami Regional Cancer Program
Miami, Florida, 33176-2197
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
Miami Beach, Florida, 33140
About this study
Official title: Phase I/II Trial of Arsenic Trioxide (As2O3) With Ascorbic Acid in the Treatment of Relapsed/Refractory Multiple Myeloma
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vitamin C may increase the effectiveness of arsenic trioxide by making cancer cells more sensitive to the drug.
PURPOSE: Phase I/II trial to determine the effectiveness of arsenic trioxide plus vitamin C in treating patients who have recurrent or refractory multiple myeloma.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of arsenic trioxide when administered with ascorbic acid in patients with recurrent or refractory multiple myeloma.
- Determine the therapeutic efficacy of this treatment combination in these patients.
- Determine the expression of MDR and Bcl-xL genes and the intracellular levels of GSH in these patients before and after this treatment regimen and assess whether these measures have prognostic value.
OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide.
- Phase I: Patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over 5-10 minutes on days 1-5 weekly for 5 weeks. Treatment continues every 7 weeks for up to 6 courses 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 reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive the MTD of arsenic trioxide with ascorbic acid as outlined above.
Patients are followed monthly for up to 5 years.
PROJECTED ACCRUAL: A total of 31-43 patients (6-18 for phase I and 16-25 for phase II) will be accrued for this study within 2.5 years.
- Being tested
- ascorbic acid, arsenic trioxide
- Keywords
- refractory multiple myeloma, stage II multiple myeloma, stage III 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
arsenic trioxideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course
Secondary outcomes (1)
Toxicity as measured by CTCAE criteria
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startJun 2000
- Primary completionMay 2006
- Study completionMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Kelvin Lee, MD, Study chair, University of Miami Sylvester Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006021
- Sponsor's protocol ID
- 20000156
- Other IDs
- CDR0000068033, SCCC-2000010
- Status last verified
- Dec 2016
- First submitted
- 5 Jul 2000
- Last updated
- 15 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bahlis NJ, McCafferty-Grad J, Jordan-McMurry I, Neil J, Reis I, Kharfan-Dabaja M, Eckman J, Goodman M, Fernandez HF, Boise LH, Lee KP. Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin Cancer Res. 2002 Dec;8(12):3658-68.
PubMed 12473574
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Arsenic Trioxide (As2O3) With Ascorbic Acid in the Treatment of Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00006021
- Acronym / sponsor ID
- 20000156
- Keywords
- refractory multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2000
- Primary completion
- May 2006 (actual)
- Study completion
- Mar 2007 (actual)
- First posted
- 27 Jan 2003 (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 use different ways to stop cancer cells from dividing so they stop growing or die. Vitamin C may increase the effectiveness of arsenic trioxide by making cancer cells more sensitive to the drug.
PURPOSE: Phase I/II trial to determine the effectiveness of arsenic trioxide plus vitamin C in treating patients who have recurrent or refractory multiple myeloma.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of arsenic trioxide when administered with ascorbic acid in patients with recurrent or refractory multiple myeloma.
- Determine the therapeutic efficacy of this treatment combination in these patients.
- Determine the expression of MDR and Bcl-xL genes and the intracellular levels of GSH in these patients before and after this treatment regimen and assess whether these measures have prognostic value.
OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide.
- Phase I: Patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over 5-10 minutes on days 1-5 weekly for 5 weeks. Treatment continues every 7 weeks for up to 6 courses 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 reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive the MTD of arsenic trioxide with ascorbic acid as outlined above.
Patients are followed monthly for up to 5 years.
PROJECTED ACCRUAL: A total of 31-43 patients (6-18 for phase I and 16-25 for phase II) will be accrued for this study within 2.5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 120 years
- 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 acid | Dietary supplement | – |
| arsenic trioxide | Drug | – |
Primary outcome
Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course
1 secondary outcome
Toxicity as measured by CTCAE criteria
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 15 Dec 2016.
- Results publication: PubMed 12473574Bahlis NJ, McCafferty-Grad J, Jordan-McMurry I, Neil J, Reis I, Kharfan-Dabaja M, Eckman J, Goodman M, Fernandez HF, Boise LH, Lee KP. Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin Cancer Res. 2002 Dec;8(12):3658-68.
Related trials for Multiple Myeloma and Plasma Cell Neoplasm
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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.
Kelvin Lee, MD study chair
University of Miami Sylvester Comprehensive Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ascorbic acid and arsenic trioxide in people with Multiple Myeloma and Plasma Cell Neoplasm, run by University of Miami at 4 sites 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 15 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006021, which also lists 1 linked publication.
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 15 Dec 2016.