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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.

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

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

Other trials in United States

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.

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 groups in NCT01001442
Study groupRoleWhat they receive
BT062ExperimentalBT062 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.

  1. 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)

  2. 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)

  1. 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)

  2. 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).

  3. 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).

  4. 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.

  1. First posted26 Oct 2009 (estimated)
  2. Study startAug 2010
  3. Primary completionJul 2014
  4. Study completionMar 2016

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
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
Data monitoring committee
Yes

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?

On the ClinicalTrials.gov record for NCT01001442.

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.

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