Drug/Agent Toxicity by Tissue/OrganPhase 1NCT00317798
Antithymocyte Globulin and Sirolimus in Treating Patients With Relapsed Multiple Myeloma
A Phase 1 study testing anti-thymocyte globulin and sirolimus in people with Drug/Agent Toxicity by Tissue/Organ and Multiple Myeloma and Plasma Cell Neoplasm, run by University of Rochester at 1 site in United States.
Trial summary
RATIONALE: Biological therapies, such as antithymocyte globulin may stimulate the immune system in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug/Agent Toxicity by Tissue/Organ, Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- anti-thymocyte globulin and sirolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Apr 2011
- 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:
- Previously diagnosed multiple myeloma (MM) based on standard criteria
- Soft tissue (not bone only) plasmacytomas allowed
- Measurable disease, meeting both of the following criteria:
- Monoclonal population of plasma cell in the bone marrow
- Quantifiable serum and/or urine monoclonal protein (i.e., generally, but not exclusively, IgG > 1 g/dL, IgA > 0.5 g/dL, or urine light-chain excretion ≥ 200 mg/24 hours)
- Steroid-refractory disease, defined as less than a minimum response to prior high-dose glucocorticoid therapy
- Minimal response requires all of the following criteria:
- 25-49% reduction in the level of serum monoclonal paraprotein maintained for ≥ 6 weeks
- 50-89% reduction in 24-hour urinary light-chain excretion, but still > 200 mg/24 hours, maintained for ≥ 6 weeks
- 25-49% reduction in the size of soft tissue plasmacytomas (clinically or by CT scan or MRI)
- No increase in size or number of lytic bone lesions
- High-dose glucocorticoid therapy defined as 480 mg dexamethasone (or equivalent) alone or as part of a vincristine, doxorubicin, and dexamethasone regimen
- Must have undergone autologous transplantation OR received ≥ 2 conventional lines of therapy
- Currently requiring therapy for progressive disease, as indicated by any of the following criteria:
- 25% increase in paraprotein
- Development of new or progression of pre-existing lytic bone lesions or soft tissue plasmacytomas
- Hypercalcemia not attributable to any other cause
- Relapse from complete remission
- No nonsecretory MM
PATIENT CHARACTERISTICS:
- Zubrod performance status 0-2
- 3-4 allowed if, in the opinion of the investigator, secondary to MM-related bone pain
- Life expectancy ≥ 3 months
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Bilirubin ≤ 1.5 times ULN
- Calcium < 14 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- Hepatitis B surface antigen and hepatitis C antibody negative
- No known history of allergy to rabbit proteins
- No history of cardiac amyloidosis
- No poorly controlled hypertension, diabetes mellitus, coronary artery disease, or other serious medical or psychiatric illness
- No myocardial infarction within the past 6 weeks
- No New York Heart Association class III or IV heart failure
- No uncontrolled angina
- No severe uncontrolled ventricular arrhythmias
- No evidence of acute ischemia or active conduction system abnormality by electrocardiogram
- No active systemic infection requiring treatment unless adequately controlled with appropriate antimicrobial therapy (e.g., treated central line infection)
- No acute viral illness
- No pathologic fractures or symptomatic hyperviscosity
- No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, cervical cancer in situ, or any other cancer with a disease-free status for ≥ 3 years
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 8 weeks since prior immunotherapy or antibody therapy
- At least 4 weeks since prior major surgery (except for kyphoplasty)
- At least 3 weeks since prior conventional chemotherapy or radiotherapy for MM
- At least 3 weeks since prior bortezomib, thalidomide, or clarithromycin for MM
- No prior anti-thymocyte globulin
- No concurrent radiotherapy
- No other concurrent antineoplastic therapy with known activity against MM, including clarithromycin
- No other concurrent investigational agents
Trial locations and contacts
1 site in 1 country.
United States1 site
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, 14642
About this study
Official title: A Pilot, Phase-I Trial of Rabbit Anti-Thymocyte Globulin (rATG, Thymoglobulin™) in Combination With Rapamycin in Relapsed Multiple Myeloma (MM)
RATIONALE: Biological therapies, such as antithymocyte globulin may stimulate the immune system in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It may also prevent or reduce the side effects of antithymocyte globulin. Giving antithymocyte globulin together with sirolimus may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of antithymocyte globulin when given together with sirolimus in treating patients with relapsed multiple myeloma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the safety and tolerability, in terms of clinical and laboratory toxicity, of anti-thymocyte globulin (ATG) combined with sirolimus in patients with relapsed multiple myeloma.
- Determine the dose-limiting toxicity of this regimen in these patients.
- Determine the maximum tolerated dose of ATG when administered with sirolimus in these patients.
Secondary
- Determine the clinical activity of this regimen, in terms of measurability of improvement in clinical benefits, in these patients.
- Assess patients for sensitivity of CD 138^-positive myeloma cells to ATG prior to treatment.
- Determine the pharmacokinetics, in terms of ATG levels in blood and bone marrow, in these patients.
- Assess the binding capability of ATG to bone marrow resident myeloma cells.
- Determine if an ATG-resistant clone emerges after treatment.
OUTLINE: This is an open-label, pilot, dose-escalation study of anti-thymocyte globulin (ATG).
Patients receive ATG IV over 6-12 hours for 4, 6, or 8 days and oral sirolimus once daily on days 1-30 in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ATG 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. At least 6 patients are treated at the MTD.
Bone marrow aspirates and blood samples are collected at baseline and periodically during study treatment for drug sensitivity and pharmacokinetic studies.
After completion of study treatment, patients are followed every 3 weeks for up to 2 months and then monthly thereafter.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
- Being tested
- anti-thymocyte globulin, sirolimus
- Keywords
- drug/agent toxicity by tissue/organ, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma
- Medical subject headings
- Drug-Related Side Effects and Adverse Reactions, Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
Escalating doses of rATG,intravenously, starting at 6 mg/kg to a maximum of 14.5 mg/kg. Rapamycin is given orally, starting at a dose of 1 mg daily beginning on day 1 and terminating on day 30. The dose of rapamycin was adjusted to maintain a constant blood level of 4-6 ng/ml in all subjects
sirolimusDrug
escalating doses of rATG, intravenously, starting at 6 mg/kg to a maximum of 14.5 mg/kg. Rapamycin is given orally, starting at a dose of 1 mg daily beginning on day 1 and terminating on day 30. The dose of rapamycin was adjusted to maintain a constant blood level of 4-6 ng/ml in all subjects
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity and maximum tolerated dose
Measured: Duration of the study
Secondary outcomes (2)
Relapse rates as measured by standard response criteria
Measured: Duration of the study
Laboratory correlative studies
Measured: During treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2006 (estimated)
- Study startApr 2006
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug/Agent Toxicity by Tissue/OrganStudies of the same condition, open and under way.
- More trials run by University of RochesterThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, JJ Ifthikharuddin, University of Rochester
- Investigators
- J. J. Ifthikharuddin, MD, Principal investigator, James P. Wilmot Cancer CenterMartin S. Zand, MD, PhD, Principal investigator, James P. Wilmot Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00317798
- Sponsor's protocol ID
- CDR0000480087
- Other IDs
- URCC-U11405, GENZ-URCC-U11405
- Status last verified
- Aug 2011
- First submitted
- 24 Apr 2006
- Last updated
- 30 Aug 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot, Phase-I Trial of Rabbit Anti-Thymocyte Globulin (rATG, Thymoglobulin™) in Combination With Rapamycin in Relapsed Multiple Myeloma (MM)
- ClinicalTrials.gov ID
- NCT00317798
- Acronym / sponsor ID
- CDR0000480087
- Keywords
- drug/agent toxicity by tissue/organ, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- Apr 2006
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 25 Apr 2006 (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: Biological therapies, such as antithymocyte globulin may stimulate the immune system in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It may also prevent or reduce the side effects of antithymocyte globulin. Giving antithymocyte globulin together with sirolimus may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of antithymocyte globulin when given together with sirolimus in treating patients with relapsed multiple myeloma.
Detailed description
OBJECTIVES:
Primary
- Determine the safety and tolerability, in terms of clinical and laboratory toxicity, of anti-thymocyte globulin (ATG) combined with sirolimus in patients with relapsed multiple myeloma.
- Determine the dose-limiting toxicity of this regimen in these patients.
- Determine the maximum tolerated dose of ATG when administered with sirolimus in these patients.
Secondary
- Determine the clinical activity of this regimen, in terms of measurability of improvement in clinical benefits, in these patients.
- Assess patients for sensitivity of CD 138^-positive myeloma cells to ATG prior to treatment.
- Determine the pharmacokinetics, in terms of ATG levels in blood and bone marrow, in these patients.
- Assess the binding capability of ATG to bone marrow resident myeloma cells.
- Determine if an ATG-resistant clone emerges after treatment.
OUTLINE: This is an open-label, pilot, dose-escalation study of anti-thymocyte globulin (ATG).
Patients receive ATG IV over 6-12 hours for 4, 6, or 8 days and oral sirolimus once daily on days 1-30 in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ATG 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. At least 6 patients are treated at the MTD.
Bone marrow aspirates and blood samples are collected at baseline and periodically during study treatment for drug sensitivity and pharmacokinetic studies.
After completion of study treatment, patients are followed every 3 weeks for up to 2 months and then monthly thereafter.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
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 |
|---|---|---|
| anti-thymocyte globulinEscalating doses of rATG,intravenously, starting at 6 mg/kg to a maximum of 14.5 mg/kg. Rapamycin is given orally, starting at a dose of 1 mg daily beginning on day 1 and terminating on day 30. The dose of rapamycin was adjusted to maintain a constant blood level of 4-6 ng/ml in all subjects | Biological | – |
| sirolimusescalating doses of rATG, intravenously, starting at 6 mg/kg to a maximum of 14.5 mg/kg. Rapamycin is given orally, starting at a dose of 1 mg daily beginning on day 1 and terminating on day 30. The dose of rapamycin was adjusted to maintain a constant blood level of 4-6 ng/ml in all subjects | Drug | – |
Primary outcome
Dose-limiting toxicity and maximum tolerated dose
Time frame: Duration of the study
2 secondary outcomes
Relapse rates as measured by standard response criteria
Time frame: Duration of the study
Laboratory correlative studies
Time frame: During treatment
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 30 Aug 2011.
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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.
J. J. Ifthikharuddin, MD principal investigator
James P. Wilmot Cancer Center
Martin S. Zand, MD, PhD principal investigator
James P. Wilmot Cancer Center
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 anti-thymocyte globulin and sirolimus in people with Drug/Agent Toxicity by Tissue/Organ and Multiple Myeloma and Plasma Cell Neoplasm, run by University of Rochester 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 30 Aug 2011. 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?
Dose-limiting toxicity and maximum tolerated dose (time frame: Duration of the study). 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 30 Aug 2011.