Multiple MyelomaPhase 1/2NCT01001442
Safety and Dose Determining Multi-dose Study of BT062 in Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1/2 study testing BT062 in people with Multiple Myeloma, run by Biotest Pharmaceuticals Corporation at 5 sites in United States.
Trial summary
This Phase I/IIa clinical study is to test safety and anti-tumor activity of BT062 to define the best dose in treating patients with relapsed or refractory multiple myeloma with multiple doses of BT062. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- BT062
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 5 sitesUnited States
- Study dates
- Aug 2010to Mar 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Diagnosis of active multiple myeloma according to the International Myeloma Working Group diagnostic criteria
- Relapsed or relapsed/refractory multiple myeloma
- Previous treatment with both an immunomodulator and a proteosome inhibitor therapy
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (Zubrod) ≤ 2
- Ability to understand and willingness to sign a written informed consent document
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- Ability to adhere with the study visit schedule and other protocol procedures
- Life expectancy of ≥ 12 weeks
- Normal organ and marrow function
Who cannot join
- Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to day 1 or those who have not recovered from AEs due to agents administered more than 3 weeks earlier
- Treatment with another investigational agent during the study or within 4 weeks before day 1
- Major surgery within 4 weeks before day 1 (this does not include placement of vascular access device or tumor biopsies)
- Antineoplastic therapy with biological agents within 2 weeks before day 1
- Known HAHAs, HACAs, or HAMAs in response to previous MAb therapy
- Previous treatment with BT062
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- Malignancy within 3 years before day 1, other than the trial indication multiple myeloma and excluding treated non-melanoma skin cancer, superficial bladder cancer and carcinoma in-situ of the cervix
- Severe diseases of skin, colon, esophagus, or eye within 1 year before day 1, as judged by the Investigator
- Severe infections necessitating use of antibiotics / antivirals during the screening period
- Clinically relevant active infection including active hepatitis B or C or human immunodeficiency virus (HBV, HCV, or HIV) or any other concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for enrollment into this study
- Acute or relevant abnormalities in electrocardiogram (ECG), as judged by the Investigator. These abnormalities can be defined as recent myocardial infarction, uncontrolled cardiac arrhythmias and/or pronounced disturbances of the electrical conduction system of the heart.
- Significant cardiac disease such as recent myocardial infarction (≤ 6 months prior to day 1), unstable angina, uncontrolled congestive heart failure, uncontrolled hypertension (recurrent or persistent increases in systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 110 mm Hg), uncontrolled cardiac arrhythmias, grade 3 (Lown Criteria) or greater cardiac toxicity from prior chemotherapy
- History of clinically significant drug or alcohol abuse
- Unwillingness or inability to adhere to the requirements of the study
- Concomitant therapy with corticosteroids (except as indicated in low dose for other medical conditions such as inhaled steroid for asthma, topical use, or as premedication for administration of certain medications (including BT062) or blood products and for treatment of infusion reactions if needed)
- Concomitant antineoplastic therapies including chemotherapy, radiotherapy, or biological agents during the study
- Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he or she are included in the study
- Breast-feeding
- Unwillingness to use an effective contraceptive method during the study and at least 3 months after administration of study drug - unless subject is naturally infertile. (Acceptable contraceptive methods include oral or injectable contraceptives, intrauterine devices (IUD), double-barrier method, contraceptive patch, surgical sterilization, or condoms).
- Positive serum or urine pregnancy test
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263
The University of Chicago
Chicago, Illinois, 60637
The Mount Sinai School of Medicine
New York, New York, 10029
About this study
Official title: A Phase I/IIa Multi-Dose Escalation Study to Evaluate Maximum Tolerated Dose (MTD), Pharmacokinetics (PK), Safety and Efficacy of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma
This Phase I/IIa clinical study is to test safety and anti-tumor activity of BT062 to define the best dose in treating patients with relapsed or refractory multiple myeloma with multiple doses of BT062.
Read the detailed description
Phase I/IIa, open-label, 3 + 3 multi-dose escalation study. The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD.
The Phase IIa part was to include the MTD/recommended phase II dose (RPTD) expansion cohort in which descriptive statistical methods for evaluation of response, time to event endpoints, and safety were to be performed.
35 subjects in the Safety population, 34 subjects in the ITT and PP populations.
- Conditions
- Multiple Myeloma
- Being tested
- BT062
- Keywords
- Multiple myeloma, Relapsed, Refractory
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BT062Drug
Also called Indatuximab ravtansine
intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| BT062 | Experimental | BT062 was to be administered as single-dose IV infusions via a 0.22 μm in-line filter preferably in a forearm vein, according to medically accepted procedures on Days 1, 8, and 15 of each 28-day cycle. Alternatively BT062 may have been administered through a central venous line or a peripherally inserted central catheter (PICC). Other administration routes were only to be allowed after approval from Biotest. Each subject was to be monitored carefully for the effects of exposure to BT062. No subject was to have received more than 3 doses of BT062 per 28-day treatment cycle. Receives: Drug: BT062 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicities (DLT) - Number of Participants With at Least 1 DLT
The primary safety variable was to determine the incidence of DLTs in subjects with relapsed or relapsed/refractory multiple myeloma treated with BT062.
Measured: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)
Maximum Tolerated Dose (MTD)
The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD.
Only DLTs occurring in cycle 1 for each subject were counted in the dose escalation decisions.
Three subjects were treated at the first or newest dose level as available. If none of the 3 subjects experienced a DLT during Cycle 1, three subjects could be treated at the next dose level as available.
In case of a DLT the cohort was expanded to up to 6 subjects. If not more than 1 of these 6 subjects experienced a DLT during Cycle 1, a first subject could be treated at the next dose level.
If 2 or more of the 6 subjects experienced a DLT during Cycle 1 the dose escalation was stopped.
The highest dose level at which < 2 of 6 subjects experienced a DLT is defined as the MTD.
Measured: First 28-day cycle
Secondary outcomes (4)
Qualitative and Quantitative Toxicities of BT062
Qualitative and quantitative toxicities assessed by incidence of adverse events and by clinically significant changes in the patient's physical examination, vital signs, and clinical laboratory results.
The incidence of treatment emergent adverse events (TEAEs), including serious adverse events (SAEs).
Measured: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)
Multi-dose Pharmacokinetics Properties of BT062 - Cmax
Multi-dose Pharmacokinetics properties of BT062 after intravenous (IV) Administration of escalating doses of BT062 as assessed by measuring intact BT062 conjugate.
Please note that not all subjects reached Cycle 4 due to early termination . A lower number of samples could be analyzed for Cycle 4.
Measured: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months).
Anti-tumor Activity of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma by Number of Participants With Objective Response(ORR) and/or Clinial Benefit(CBR) Based on the International Myeloma Working Group Uniform Response Criteria
sCR:CR+normal FLC+absence of clonal cells in BM; CR:Negative immunofixation,disappearance of soft tissue plasmacytomas +≤5% plasma cells in BM+normal FLC; VGPR:M-protein detectable by immunofixation,not on electrophoresis or 90% or greater reduction in serum M-protein+urine M-protein level <100mg per 24h,>90% decrease in the difference between involved/uninvolved FLC; PR:≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h or ≥50% decrease in the difference between involved/uninvolved FLC or ≥50% reduction in plasma cells, provided baseline bone marrow plasma cell percentage was ≥30%, ≥50% size reduction of soft tissue plasmacytomas; MR:25%-49% reduction of serum M-protein+reduction in 24h urinary M-protein by 50-89%(still >200 mg/24h),25-49% soft tissue plasmacytomas size reduction,no increase in size or number of lytic bone lesions; SD:no response or PD ORR: %of subjects with MR+PR+VGPR+CR+sCR CBR:ORR + %of subjects with SD.
Measured: On day 1 of each treatment cycle (on a monthly basis) starting with first study drug administration until Close Out visit (average 3.84 months).
Time to Progression (TTP), Progression Free Survival (PFS) and Overall Survival (OS)
Progressive disease
Requires any one or more of the following:
Increase of ≥ 25% from baseline in
- Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL) (increases of ≥ 1 g/dL are sufficient to define relapse if starting M-component is ≥ 5 g/dL).
- Urine M-component and/or (the absolute increase must be ≥ 200mg/24h).
Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL.
Bone marrow plasma cell percentage: the absolute % must be ≥ 10% (relapse form CR as a 5% cutoff instead of 10%).
Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas.
Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/l) that can be attributed solely to the plasma cell proliferative disorder.
Measured: Starting with first study drug administration until death or 3 years from first study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2009 (estimated)
- Study startAug 2010
- Primary completionJul 2014
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biotest Pharmaceuticals Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biotest
- Responsible party
- Sponsor
- Investigators
- Kenneth C. Anderson, MD, Study director, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01001442
- Sponsor's protocol ID
- 975
- Status last verified
- Jan 2018
- First submitted
- 22 Oct 2009
- Last updated
- 30 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Multi-Dose Escalation Study to Evaluate Maximum Tolerated Dose (MTD), Pharmacokinetics (PK), Safety and Efficacy of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01001442
- Acronym / sponsor ID
- 975
- Conditions
- Multiple Myeloma
- Keywords
- Multiple myeloma, Relapsed, Refractory
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Biotest Pharmaceuticals CorporationIndustry (pharma, biotech, devices)
- Collaborators
- Biotest
- Study start
- Aug 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 26 Oct 2009 (estimated)
- Results
- Posted 8 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase I/IIa clinical study is to test safety and anti-tumor activity of BT062 to define the best dose in treating patients with relapsed or refractory multiple myeloma with multiple doses of BT062.
Detailed description
Phase I/IIa, open-label, 3 + 3 multi-dose escalation study. The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD.
The Phase IIa part was to include the MTD/recommended phase II dose (RPTD) expansion cohort in which descriptive statistical methods for evaluation of response, time to event endpoints, and safety were to be performed.
35 subjects in the Safety population, 34 subjects in the ITT and PP populations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BT062 | Experimental | Drug: BT062BT062 was to be administered as single-dose IV infusions via a 0.22 μm in-line filter preferably in a forearm vein, according to medically accepted procedures on Days 1, 8, and 15 of each 28-day cycle. Alternatively BT062 may have been administered through a central venous line or a peripherally inserted central catheter (PICC). Other administration routes were only to be allowed after approval from Biotest. Each subject was to be monitored carefully for the effects of exposure to BT062. No subject was to have received more than 3 doses of BT062 per 28-day treatment cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis of active multiple myeloma according to the International Myeloma Working Group diagnostic criteria
- Relapsed or relapsed/refractory multiple myeloma
- Previous treatment with both an immunomodulator and a proteosome inhibitor therapy
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (Zubrod) ≤ 2
Key exclusion criteria (20 listed)
- Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to day 1 or those who have not recovered from AEs due to agents administered more than 3 weeks earlier
- Treatment with another investigational agent during the study or within 4 weeks before day 1
- Major surgery within 4 weeks before day 1 (this does not include placement of vascular access device or tumor biopsies)
- Antineoplastic therapy with biological agents within 2 weeks before day 1
- Known HAHAs, HACAs, or HAMAs in response to previous MAb therapy
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 |
|---|---|---|
| BT062Also: Indatuximab ravtansineintravenous administration | Drug | BT062 |
Primary outcome
Dose Limiting Toxicities (DLT) - Number of Participants With at Least 1 DLT
Time frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)
The primary safety variable was to determine the incidence of DLTs in subjects with relapsed or relapsed/refractory multiple myeloma treated with BT062.
Maximum Tolerated Dose (MTD)
Time frame: First 28-day cycle
The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD. Only DLTs occurring in cycle 1 for each subject were counted in the dose escalation decisions. Three subjects were treated at the first or newest dose level as available. If none of the 3 subjects experienced a DLT during Cycle 1, three subjects could be treated at the next dose level as available. In case of a DLT the cohort was expanded to up to 6 subjects. If not more than 1 of these 6 subjects experienced a DLT during Cycle 1, a first subject could be treated at the next dose level. If 2 or more of the 6 subjects experienced a DLT during Cycle 1 the dose escalation was stopped. The highest dose level at which < 2 of 6 subjects experienced a DLT is defined as the MTD.
4 secondary outcomes
Qualitative and Quantitative Toxicities of BT062
Time frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)
Multi-dose Pharmacokinetics Properties of BT062 - Cmax
Time frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months).
Anti-tumor Activity of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma by Number of Participants With Objective Response(ORR) and/or Clinial Benefit(CBR) Based on the International Myeloma Working Group Uniform Response Criteria
Time frame: On day 1 of each treatment cycle (on a monthly basis) starting with first study drug administration until Close Out visit (average 3.84 months).
Time to Progression (TTP), Progression Free Survival (PFS) and Overall Survival (OS)
Time frame: Starting with first study drug administration until death or 3 years from first study treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kenneth C. Anderson, MD study director
Dana-Farber Cancer Institute
5 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 BT062 in people with Multiple Myeloma, run by Biotest Pharmaceuticals Corporation at 5 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?
The sponsor lists 9 inclusion and 20 exclusion criteria. 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 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
Yes. Results are posted in the registry (first posted 8 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Toxicities (DLT) - Number of Participants With at Least 1 DLT (time frame: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)). The study lists 2 primary outcomes in all. 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 Jul 2019; AzTrials last refreshed its copy on 6 Nov 2026.