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The objective of the first part of the study is to determine a safe dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. The objectives of the second part of the study are to compare the safety and efficacy of TRU-016 in combination with bendamustine to bendamustine alone in patients with relapsed CLL.
This study consisted of two parts. The initial dose escalation stage was a Phase 1b study evaluating the safety and tolerability of two doses of TRU-016 administered in combination with bendamustine to patients with relapsed chronic lymphocytic leukemia (CLL). In the randomized Phase 2 stage of the study, the efficacy and safety of the selected dose of 20 mg/kg TRU-016 combined with bendamustine was compared to bendamustine alone. The pharmacokinetics and pharmacodynamics of TRU-016 and the development of antibodies to TRU-016 were evaluated in both phases of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1: 15 mg/kg TRU-016 + Bendamustine | Experimental | TRU-016 (15 mg/kg) and bendamustine (70 mg/m2), n = 6 patients |
|
| Phase 1: 20 mg/kg TRU-016 + Bendamustine | Experimental | TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 6 patients |
|
| Phase 2: TRU-016 and bendamustine | Experimental | TRU-016 (20 mg/kg) and bendamustine (70 mg/m2), n = 32 patients |
|
| Phase 2: Bendamustine | Active Comparator | Bendamustine (70 mg/m2), n = 33 patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TRU-016 and bendamustine | Drug | TRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
| Measure | Description | Time Frame |
|---|---|---|
| Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria | Patients had full clinical response assessment monthly during treatment, at the end of treatment (EOT) visit, 30 and 60 days after the EOT visit, and subsequently every 3 months until the earliest of progression of CLL, death, initiation of new therapy, withdrawal from the study, or completion of 18 months of follow-up evaluations. Clinical response assessment included physical examination with measurement of spleen, liver, and lymph nodes, disease-related symptoms, and laboratory measurements, specifically complete blood count (CBC) with differential. | 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Response Per NCI Criteria | Overall response rate per National Cancer Institute (NCI) Working group criteria. | 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Scott Stromatt, MD | Emergent Product Development Seattle LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding sites for this trial call (919) 465-4648 | Denver | Colorado | 80218 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27977057 | Background | Robak T, Hellmann A, Kloczko J, Loscertales J, Lech-Maranda E, Pagel JM, Mato A, Byrd JC, Awan FT, Hebart H, Garcia-Marco JA, Hill BT, Hallek M, Eisenfeld AJ, Stromatt SC, Jaeger U. Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia. Br J Haematol. 2017 Feb;176(4):618-628. doi: 10.1111/bjh.14464. Epub 2016 Dec 15. |
| Label | URL |
|---|---|
| Otlertuzumab and Bendamustine in Relapsed CLL | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1 15 mg/kg | TRU-016 (15 mg/kg), weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles and bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
| FG001 | Phase 1 20 mg/kg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Bendamustine | Drug | Bendamustine at 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
|
| 15 mg/kg TRU-016 and bendamustine | Drug | TRU-016 at 15 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
|
| 20 mg/kg TRU-016 and bendamustine | Drug | TRU-016 at 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
|
| For additional information regarding sites for this trial call (919) 465-4648 |
| Augusta |
| Georgia |
| 30912 |
| United States |
| For additional information regarding sites for this trial call (919) 465-4648 | Chicago | Illinois | 60637 | United States |
| For additional information regarding sites for this trial call (919) 465-4648 | Hackensack | New Jersey | 07601 | United States |
| For additional information regarding sites for this trial call (919) 465-4648 | Syracuse | New York | 13210 | United States |
| For additional information regarding sites for this trial call (919) 465-4648 | Durham | North Carolina | 27710 | United States |
| For additional information regarding sites for this trial call (919) 465-4648 | Cleveland | Ohio | 44195 | United States |
| For additional information regarding sites for this trial call (919) 465-4648 | Columbus | Ohio | 43210 | United States |
| For additional information regarding sites for this trial call (919) 465-4648 | Seattle | Washington | 98109 | United States |
| For additional information regarding sites for this trial call (919) 465-4648 | Vienna | Austria |
| For additional information regarding sites for this trial call (919) 465-4648 | Bremen | Germany |
| For additional information regarding sites for this trial call (919) 465-4648 | Cologne | Germany |
| For additional information regarding sites for this trial call (919) 465-4648 | Frankfurt | Germany |
| For additional information regarding sites for this trial call (919) 465-4648 | Göttingen | Germany |
| For additional information regarding sites for this trial call (919) 465-4648 | Kiel | Germany |
| For additional information regarding sites for this trial call (919) 465-4648 | Mainz | Germany |
| For additional information regarding sites for this trial call (919) 465-4648 | Mutlangen | Germany |
| For additional information regarding sites for this trial call (919) 465-4648 | Regensburg | Germany |
| For additional information regarding sites for this trial call (919) 465-4648 | Bialystok | Poland |
| For additional information regarding sites for this trial call (919) 465-4648 | Gdansk | Poland |
| For additional information regarding sites for this trial call (919) 465-4648 | Lodz | Poland |
| For additional information regarding sites for this trial call (919) 465-4648 | Poznan | Poland |
| For additional information regarding sites for this trial call (919) 465-4648 | Warsaw | Poland |
| For additional information regarding sites for this trial call (919) 465-4648 | Madrid | Spain |
| For additional information regarding sites for this trial call (919) 465-4648 | Navarre | Spain |
TRU-016 (20 mg/kg), weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles and bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles
| FG002 | Phase 2 TRU-016 and Bendamustine | Patients in the combination arm received otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles. In both arms, bendamustine (70 mg/m2) was administered IV on Days 1 and 2 of each cycle for up to six 28-day cycles. |
| FG003 | Phase 2 Bendamustine | Patients in the bendamustine arm received bendamustine (70 mg/m2) administered IV on Days 1 and 2 of each cycle for up to six 28-day cycles. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
patients with relapsed chronic lymphocytic leukemia
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1: 15 mg/kg TRU-016 | TRU-016 (15 mg/kg) and bendamustine (70 mg/m2) TRU-016 and bendamustine: TRU-016 (20 mg/kg) weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
| BG001 | Phase 1: 20 mg/kg TRU-016 | TRU-016 (20 mg/kg) and bendamustine (70 mg/m2) TRU-016 and bendamustine: TRU-016 (20 mg/kg) weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
| BG002 | Phase 2: TRU-016 and Bendamustine | TRU-016 (20 mg/kg) and bendamustine (70 mg/m2) TRU-016 and bendamustine: TRU-016 (20 mg/kg) weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
| BG003 | Phase 2: Bendamustine | Bendamustine alone (70 mg/m2) Bendamustine: 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Response Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria | Patients had full clinical response assessment monthly during treatment, at the end of treatment (EOT) visit, 30 and 60 days after the EOT visit, and subsequently every 3 months until the earliest of progression of CLL, death, initiation of new therapy, withdrawal from the study, or completion of 18 months of follow-up evaluations. Clinical response assessment included physical examination with measurement of spleen, liver, and lymph nodes, disease-related symptoms, and laboratory measurements, specifically complete blood count (CBC) with differential. | Treated patients | Posted | Number | percentage of patients | 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years |
|
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Response Per NCI Criteria | Overall response rate per National Cancer Institute (NCI) Working group criteria. | Safety data for all patients who received any study drug and efficacy data for randomized patients who received some study treatment and have some post baseline data are presented here. | Posted | Number | percentage of patients | 1 and 2 months after end of treatment, then every 3 months until disease progression, death, initiation of new therapy, study withdrawal, or 2 years |
|
Adverse event information was collected during the clinical trial from the time consent was given through 30 days post last drug infusion.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1: 15 mg/kg | TRU-016 (15 mg/kg), weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles | 3 | 6 | 6 | 6 | ||
| EG001 | Phase 1: 20 mg/kg | TRU-016 (20 mg/kg), weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles | 1 | 6 | 6 | 6 | ||
| EG002 | Phase 2: TRU-016 and Bendamustine | TRU-016 (20 mg/kg) and bendamustine (70 mg/m2) TRU-016 and bendamustine: TRU-016 (20 mg/kg) weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles | 10 | 32 | 24 | 32 | ||
| EG003 | Phase 2:Bendamustine | Bendamustine alone (70 mg/m2) Bendamustine: 70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles | 15 | 33 | 25 | 33 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | Medra 8.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Aplasia pure red cell | Blood and lymphatic system disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Autoimmune haemolytic anaemia | Blood and lymphatic system disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Bronchopneumonia | Infections and infestations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Thrombophlebitis septic | Infections and infestations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (8.1) | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Chronic lymphocytic leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (8.1) | Non-systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (8.1) | Non-systematic Assessment |
| |
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA (8.1) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (8.1) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA | Non-systematic Assessment |
| |
| Hypogammaglobulinaemia | Immune system disorders | MedDRA | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA | Non-systematic Assessment |
| |
| Hypokalaemia | Investigations | MedDRA | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scott C. Stromatt | Emergent BioSolutions | 206-859-6675 | sstromatt@ebsi.com |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C547387 | TRU 016 |
| D000069461 | Bendamustine Hydrochloride |
| ID | Term |
|---|---|
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG003 | Phase 1: 20 mg/kg TRU-016 +Bendamustine | TRU-016 and bendamustine: TRU-016 (n = 6 patients), 20 mg/kg, weekly by IV infusion x 2 cycles, then every 14 days x 4 cycles PLUS bendamustine (70 mg/m2 by IV infusion on Days 1 and 2 of every 28-day cycle, for 6 cycles |
|
|