Non-Hodgkin's LymphomaPhase 1NCT01452334
Safety Study of Anti-Programmed Death-Ligand 1 in Hematologic Malignancy
A Phase 1 study testing BMS-936559 (Anti PD-L1) in people with Non-Hodgkin's Lymphoma and Hodgkin Lymphoma, run by Bristol-Myers Squibb.
Trial summary
The purpose of this study is to determine the side effects of treatment with the monoclonal antibody anti-PD-L1 (BMS-936559) in subjects with compromised bone marrow function and the dose that should be recommended for use in future studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Hodgkin Lymphoma, Multiple Myeloma
- What is being tested?
- BMS-936559 (Anti PD-L1)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2011to Nov 2014
- 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
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) Performance of 0 or 1
- Subjects must have histological confirmation of relapsed or refractory hematologic malignancy
- Subjects with non-Hodgkin's lymphoma or Hodgkin lymphoma must have at least one measureable lesion as defined by lymphoma response criteria. Tumor sites that are considered measureable must not have received prior radiation therapy
- Subjects with multiple myeloma (MM) must have detectable disease as measured by presence of monoclonal immunoglobulin protein in a serum electrophoresis: IgG, IgA, IgM, (M-protein ≥ 0.5 g/dl or serum IgD M-protein ≥ 0.05 g/dl) or serum free-light chain or 24 hour urine with free light chain. Excluded are subjects with only plasmacytomas, plasma cell leukemia, or non-secretory myeloma
- Subjects with chronic myelogenous leukemia (CML) must have evidence of the Philadelphia chromosome by polymerase chain reaction (PCR) or chromosome analysis
- Life expectancy of at least 3 months
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- For subjects with lymphoma, either a formalin fixed tissue block or 7 to 15 slides of tumor sample (archival or fresh) must be available for performance of correlative studies
- Subjects must have received at least one prior chemotherapy regimen. Subjects must be off therapy for at least 4 weeks ( 2 weeks for oral agents) prior to Day 1
- Prior palliative radiation must have been completed at least 2 weeks prior to study Day 1
- Toxicities related to prior therapy must have returned to Grade 1 or less, except for alopecia. Peripheral neuropathy must be Grade 2 or less
- Adequate bone marrow function defined as:
- Absolute neutrophil count ≥ 1000/μl (stable off any growth factor within 1 week of study drug administration)
- Hemoglobin ≥ 9 g/dL (transfusion to achieve this level is permitted)
- Platelet count ≥ 50 X 103/ μl (transfusion to achieve this level is not permitted)
- Adequate renal parameters defined as Creatinine clearance (CrCl) > 40 ml/min (Cockcroft-Gault formula)
- Adequate hepatic parameters defined as:
- Aspartate aminotransferase (AST) ≤ 3 x ULN
- Alanine aminotransferase (ALT) ≤ 3 x ULN
- Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's Syndrome, who must have total bilirubin < 3.0 mg/dL and direct bilirubin < 0.5 mg/dL)
- Women of child bearing potential (WOCBP) and for at least 70 days after the last dose of investigational product
- Men and women ≥ 18 years of age
Who cannot join
- Subjects with acute leukemias, blast phase CML, T cell lymphoblastic or Burkitt lymphoma
- Subjects with a history of central nervous system involvement by hematologic malignancy or symptoms suggestive of central nervous system involvement
- Subjects with concomitant second malignancies (except adequately treated nonmelanomatous skin cancers, ductal carcinoma in situ, treated superficial bladder cancer or prostate cancer or in situ cervical cancers) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period
- Subjects with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of syndrome that requires systemic corticosteroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy
- A serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy
- Prior therapy with an anti programmed death-1 (anti-PD-1), anti Programmed death ligand 1 (anti-PD-L1), anti Programmed death ligand 2 (anti-PD-L2), anti-CD137 or anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways)
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- Non-oncology vaccine therapies for prevention of infectious diseases (eg seasonal flu vaccine, Human Papilloma Virus (HPV) vaccine) within 4 weeks of study drug administration Vaccination while on study is also prohibited except for administration of the inactivated influenza vaccine
- Prior organ allograft or allogeneic bone marrow transplantation
- Positive for human immunodeficiency virus (HIV 1/2) or known acquired immunodeficiency syndrome (AIDS)
- Positive tests for hepatitis B virus surface antigen (HBsAg), or antibody to hepatitis B core Ag or hepatitis C virus antibody (confirmed by Western Blot) or hepatitis C ribonucleic acid (RNA) in serum
- Ejection fraction less than 45% in subjects with prior anthracycline exposure
- History of Grade 4 anaphylactic reaction to monoclonal antibody therapy
- Women who are pregnant or breastfeeding
About this study
Official title: A Phase I Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Immunoregulatory Activity, and Preliminary Antitumor Activity of Anti-Programmed-Death-Ligand 1 (PD-L1) Antibody (BMS-936559) in Subjects With Relapsed or Refractory Hematologic Malignancy
The purpose of this study is to determine the side effects of treatment with the monoclonal antibody anti-PD-L1 (BMS-936559) in subjects with compromised bone marrow function and the dose that should be recommended for use in future studies.
- Being tested
- BMS-936559 (Anti PD-L1)
- Medical subject headings
- Lymphoma, Non-Hodgkin, Hodgkin Disease, Multiple Myeloma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-936559 (Anti PD-L1)Biological
Injection for infusion, Intravenous (IV), 1, 3 or 10 mg/kg, Every 2 weeks, 48-96 weeks depending on response
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: BMS-936559 | Experimental | Not described Receives: Biological: BMS-936559 (Anti PD-L1) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Measured: Weeks 1
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Measured: Weeks 2
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Measured: Weeks 3
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Measured: Weeks 6
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Measured: Every 2 weeks until 70 days after last treatment
Secondary outcomes (9)
Pharmacokinetics of BMS-936559 as measured by maximum observed serum concentration (Cmax)
Measured: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by time of maximum observed serum concentration (Tmax)
Measured: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by area under the serum concentration time curve in the dosing interval [AUC(TAU)]
Measured: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by accumulation index (AI) calculated ar ratio of the AUC(TAU) at steady state and first dose
Measured: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by serum concentration achieved at the end of dosing interval (trough concentration) (Cmin)
Measured: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by serum concentration achieved at the end of the infusion (Ceoinf)
Measured: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Antitumor activity of BMS-936559 as measured by the objective response rate, duration of response, and progression free survival
Measured: Week 4, week 12, week 20, and every 16 weeks until confirmed disease progression assessed up to Week 214
Immunogenicity of BMS-936559 as measured by the frequency of subjects with an increase in anti-drug antibody levels from baseline
Measured: Baseline, weeks 3, weeks 12, weeks 20, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Programmed death ligand 1 (PD-L1) receptor occupancy levels as measured by changes from baseline
Measured: Baseline and within the first 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionNov 2014 (estimated)
- Study completionNov 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01452334
- Sponsor's protocol ID
- CA210-003
- Status last verified
- Feb 2012
- First submitted
- 4 Oct 2011
- Last updated
- 23 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Immunoregulatory Activity, and Preliminary Antitumor Activity of Anti-Programmed-Death-Ligand 1 (PD-L1) Antibody (BMS-936559) in Subjects With Relapsed or Refractory Hematologic Malignancy
- ClinicalTrials.gov ID
- NCT01452334
- Acronym / sponsor ID
- CA210-003
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Nov 2014 (estimated)
- Study completion
- Nov 2014 (estimated)
- First posted
- 14 Oct 2011 (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.
The purpose of this study is to determine the side effects of treatment with the monoclonal antibody anti-PD-L1 (BMS-936559) in subjects with compromised bone marrow function and the dose that should be recommended for use in future studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: BMS-936559 | Experimental | Biological: BMS-936559 (Anti PD-L1) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Eastern Cooperative Oncology Group (ECOG) Performance of 0 or 1
- Subjects must have histological confirmation of relapsed or refractory hematologic malignancy
- Subjects with non-Hodgkin's lymphoma or Hodgkin lymphoma must have at least one measureable lesion as defined by lymphoma response criteria. Tumor sites that are considered measureable must not have received prior radiation therapy
- Subjects with multiple myeloma (MM) must have detectable disease as measured by presence of monoclonal immunoglobulin protein in a serum electrophoresis: IgG, IgA, IgM, (M-protein ≥ 0.5 g/dl or serum IgD M-protein ≥ 0.05 g/dl) or serum free-light chain or 24 hour urine with free light chain. Excluded are subjects with only plasmacytomas, plasma cell leukemia, or non-secretory myeloma
- Subjects with chronic myelogenous leukemia (CML) must have evidence of the Philadelphia chromosome by polymerase chain reaction (PCR) or chromosome analysis
Key exclusion criteria (13 listed)
- Subjects with acute leukemias, blast phase CML, T cell lymphoblastic or Burkitt lymphoma
- Subjects with a history of central nervous system involvement by hematologic malignancy or symptoms suggestive of central nervous system involvement
- Subjects with concomitant second malignancies (except adequately treated nonmelanomatous skin cancers, ductal carcinoma in situ, treated superficial bladder cancer or prostate cancer or in situ cervical cancers) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period
- Subjects with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of syndrome that requires systemic corticosteroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy
- A serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this 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 |
|---|---|---|
| BMS-936559 (Anti PD-L1)Injection for infusion, Intravenous (IV), 1, 3 or 10 mg/kg, Every 2 weeks, 48-96 weeks depending on response | Biological | Arm 1: BMS-936559 |
Primary outcome
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Time frame: Weeks 1
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Time frame: Weeks 2
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Time frame: Weeks 3
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Time frame: Weeks 6
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs
Time frame: Every 2 weeks until 70 days after last treatment
9 secondary outcomes
Pharmacokinetics of BMS-936559 as measured by maximum observed serum concentration (Cmax)
Time frame: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by time of maximum observed serum concentration (Tmax)
Time frame: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by area under the serum concentration time curve in the dosing interval [AUC(TAU)]
Time frame: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by accumulation index (AI) calculated ar ratio of the AUC(TAU) at steady state and first dose
Time frame: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by serum concentration achieved at the end of dosing interval (trough concentration) (Cmin)
Time frame: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Pharmacokinetics of BMS-936559 as measured by serum concentration achieved at the end of the infusion (Ceoinf)
Time frame: Within the first 22 weeks, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Antitumor activity of BMS-936559 as measured by the objective response rate, duration of response, and progression free survival
Time frame: Week 4, week 12, week 20, and every 16 weeks until confirmed disease progression assessed up to Week 214
Immunogenicity of BMS-936559 as measured by the frequency of subjects with an increase in anti-drug antibody levels from baseline
Time frame: Baseline, weeks 3, weeks 12, weeks 20, weeks 34, weeks 46, and at follow-up (35 ± 7 days after last treatment and 70-90 days since last treatment)
Programmed death ligand 1 (PD-L1) receptor occupancy levels as measured by changes from baseline
Time frame: Baseline and within the first 3 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2012.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-936559 (Anti PD-L1) in people with Non-Hodgkin's Lymphoma and Hodgkin Lymphoma, run by Bristol-Myers Squibb.
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 21 inclusion and 13 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: withdrawn, as of the sponsor's last update on 23 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, dose-limiting toxicities, laboratory test abnormalities, and changes in vital signs (time frame: Weeks 1). The study lists 5 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 23 Feb 2012.