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The main purpose of this study is to determine the maximum tolerated and efficient dose of GRASPA® in combination with polychemotherapy treatment of elderly patients with ALL, 55 years and over, Philadelphia chromosome-negative (ALL Ph-).
This open label, non randomised, multicentric and national phase IIa study was designed to evaluate the safety and efficacy of GRASPA®, a suspension of red blood cells encapsulating E. Coli L-asparaginase, at different doses and in combination with the polychemotherapy regimen recommended by the European Working Group on Adult ALL (EWALL) for frontline therapy of patients with ALL Ph-, aged 55 years old and over. Patients with a good performance status (WHO score ≤2) and a newly diagnosed ALL Ph- were treated with the backbone polychemotherapy consisting of a first 4-week induction phase comprising dexamethasone, vincristine and idarubicin, a second 4-week induction phase including cyclophosphamide, cytarabine, a 6-month consolidation phase consisting of 6 alternating cycles with methotrexate, asparaginase and folinic acid (cycles 1, 3 and 5) and high-dose cytarabine (cycles 2, 4 and 6) with Granulocyte colony stimulating factor (G-CSF) support followed by a 16-month maintenance period with mercaptopurine, methotrexate and vincristine/dexamethasone pulses. GRASPA® was administered on day 3 of induction 1 and on day 6 of induction 2 of the chemotherapy regimen.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GRASPA 50 IU/kg | Experimental | Each patient will receive GRASPA 50 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase. |
|
| GRASPA 100 IU/kg | Experimental | Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
|
| GRASPA 150 IU/kg | Experimental | Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GRASPA | Drug | Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment | The main evaluation criterion is a composite efficacy/toxicity criterion. Efficacy, assessed during induction 1: percentage of patients responding to treatment, i.e. with plasma Asn concentration ≤2µM (depleted), for a duration of at least 7 days after the administration of GRASPA® | 7 days after the first administration of GRASPA® during Induction 1 |
| Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2 | Safety: Toxicity, assessed during Induction 1 and Induction 2: according to NCI-CTCAE v3.0 August 2006, with Dose Limiting Toxicities (DLT) defined as: Grade 2 to 4 pancreatic toxicity, Grade 3 or 4 hepatic toxicity, allergic toxicity or deep cerebral thrombosis, known as potentially related to L-asparaginase; hematological toxicity defined as bone marrow blast free aplasia, 30 days following the last injection of chemotherapy, all other Grade 4 toxicities. | Induction 1 and Induction 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentrations of Asparagine | Mean plasma concentration of asparagine over time. Participants who were Below the Lower Limit of Quantification (BLLQ) were assigned a value of 0.51 μmol/L. | Induction 1 & Induction 2 |
| Plasma Concentrations of Aspartic Acid |
Not provided
Inclusion Criteria:
Exclusion Criteria:
ALL translocation(9;22) and/or BCR-ABL (Breakpoint Cluster Region-Abelson) positive
Performance status incompatible with chemotherapy treatment (WHO score >2)
Patient presenting with a general or visceral contraindication to intensive treatment including :
Prior treatment with L-asparaginase (irrespective of the form)
History of grade 3 transfusional incident (life threatening)
Patient presenting rare and/or dangerous anti-erythrocyte antibodies thus leading to the unavailability of phenotype compatible Red Blood Cells Concentrate
Patient included in another clinical trial during the last 4 weeks
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| Name | Affiliation | Role |
|---|---|---|
| Mathilde Hunault-Berger, Professor | University Hospital, Angers | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26094614 | Derived | Hunault-Berger M, Leguay T, Huguet F, Lepretre S, Deconinck E, Ojeda-Uribe M, Bonmati C, Escoffre-Barbe M, Bories P, Himberlin C, Chevallier P, Rousselot P, Reman O, Boulland ML, Lissandre S, Turlure P, Bouscary D, Sanhes L, Legrand O, Lafage-Pochitaloff M, Bene MC, Liens D, Godfrin Y, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). A Phase 2 study of L-asparaginase encapsulated in erythrocytes in elderly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL-SA2-2008 study. Am J Hematol. 2015 Sep;90(9):811-8. doi: 10.1002/ajh.24093. |
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Not applicable for this study
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| ID | Title | Description |
|---|---|---|
| FG000 | GRASPA 50 IU/kg | Each patient will receive GRASPA 50 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase. GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| FG001 | GRASPA 100 IU/kg | Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| FG002 | GRASPA 150 IU/kg | Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | GRASPA 50 IU/kg | Each patient will receive GRASPA 50 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase. GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment | The main evaluation criterion is a composite efficacy/toxicity criterion. Efficacy, assessed during induction 1: percentage of patients responding to treatment, i.e. with plasma Asn concentration ≤2µM (depleted), for a duration of at least 7 days after the administration of GRASPA® | Posted | Count of Participants | Participants | 7 days after the first administration of GRASPA® during Induction 1 |
|
The period of adverse event (AE) reporting was from the patient inclusion until the end of the product safety follow-up, reached 2 months after the last GRASPA® administration, thus theoretically corresponding to the end of the 2nd cycle of consolidation (Visit V12).
Some Adverse Events were monitored/assessed without regard to the specific Adverse Event Term (i.e. "Gastrointestinal Disorder" and "General Disorder").
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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 | GRASPA 50 IU/kg | Each patient will receive GRASPA 50 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase. GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Septic Shock | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Antithrombin III decreased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Denise Tilton, Global Head Clinical Operations & Program Management | ERYTECH Pharma | +1 857-706-1587 | dtilton@erytech.com |
Not provided
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Open label
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|
Mean plasma concentration of aspartic acid over time. |
| Induction 1 and Induction 2 |
| Plasma Concentrations of Glutamine | Mean glutamine concentration over time. | Induction 1 and Induction 2 |
| Plasma Concentrations of Glutamic Acid. | Mean glutamic acid concentration over time. | Induction 1 and Induction 2 |
| Cerebral Spinal Fluid Concentrations of Asparagine | Mean cerebral spinal fluid asparagine concentration over time. | Induction 1 and Induction 2 |
| Cerebral Spinal Fluid Concentrations of Aspartic Acid | Mean cerebral spinal fluid aspartic acid concentration | Induction 1 and Induction 2 |
| Cerebral Spinal Fluid Concentrations of Glutamine | Mean cerebral spinal fluid glutamine concentration | Induction 1 and Induction 2 |
| Cerebral Spinal Fluid Concentrations of Glutamic Acid | Mean cerebral spinal fluid glutamic acid concentration | Induction 1 and Induction 2 |
| Summary of Free Asparaginase Over Time | Induction 1 and Induction 2 |
| Summary of Encapsulated Asparaginase (U/L) Over Time | Induction 1 and Induction 2 |
| Number of Patients Positive for Anti-L-asparaginase Antibodies | Evaluation of the number of patients testing positive for anti-asparaginase antibodies. | Induction 1 and Induction 2 |
| Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2 | CR was defined using:
| 1 and 2 months |
| BG001 | GRASPA 100 IU/kg | Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| BG002 | GRASPA 150 IU/kg | Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | GRASPA 100 IU/kg | Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
| OG002 | GRASPA 150 IU/kg | Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase |
|
|
| Primary | Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2 | Safety: Toxicity, assessed during Induction 1 and Induction 2: according to NCI-CTCAE v3.0 August 2006, with Dose Limiting Toxicities (DLT) defined as: Grade 2 to 4 pancreatic toxicity, Grade 3 or 4 hepatic toxicity, allergic toxicity or deep cerebral thrombosis, known as potentially related to L-asparaginase; hematological toxicity defined as bone marrow blast free aplasia, 30 days following the last injection of chemotherapy, all other Grade 4 toxicities. | Posted | Number | DLTs | Induction 1 and Induction 2 |
|
|
|
| Secondary | Plasma Concentrations of Asparagine | Mean plasma concentration of asparagine over time. Participants who were Below the Lower Limit of Quantification (BLLQ) were assigned a value of 0.51 μmol/L. | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | μmol/L | Induction 1 & Induction 2 |
|
|
|
| Secondary | Plasma Concentrations of Aspartic Acid | Mean plasma concentration of aspartic acid over time. | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | μmol/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Plasma Concentrations of Glutamine | Mean glutamine concentration over time. | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | μmol/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Plasma Concentrations of Glutamic Acid. | Mean glutamic acid concentration over time. | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | μmol/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Cerebral Spinal Fluid Concentrations of Asparagine | Mean cerebral spinal fluid asparagine concentration over time. | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | μmol/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Cerebral Spinal Fluid Concentrations of Aspartic Acid | Mean cerebral spinal fluid aspartic acid concentration | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | μmol/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Cerebral Spinal Fluid Concentrations of Glutamine | Mean cerebral spinal fluid glutamine concentration | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | μmol/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Cerebral Spinal Fluid Concentrations of Glutamic Acid | Mean cerebral spinal fluid glutamic acid concentration | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | μmol/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Summary of Free Asparaginase Over Time | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | U/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Summary of Encapsulated Asparaginase (U/L) Over Time | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Mean | Standard Deviation | U/L | Induction 1 and Induction 2 |
|
|
|
| Secondary | Number of Patients Positive for Anti-L-asparaginase Antibodies | Evaluation of the number of patients testing positive for anti-asparaginase antibodies. | The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. | Posted | Count of Participants | Participants | Induction 1 and Induction 2 |
|
|
|
| Secondary | Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2 | CR was defined using:
| 28 patients were analyzed for CR after Induction 1 (2 pts in 50 IU/kg; 13 pts in 100 IU/kg; 13 pts in 150 IU/kg). 22 patients were analyzed for CR after Induction 2 (2 pts in 50 IU/kg; 11 pts in 100 IU/kg; 9 pts in 150 IU/kg). | Posted | Count of Participants | Participants | 1 and 2 months |
|
|
|
| 1 |
| 3 |
| 3 |
| 3 |
| 3 |
| 3 |
| EG001 | GRASPA 100 IU/kg | Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase | 2 | 13 | 13 | 13 | 13 | 13 |
| EG002 | GRASPA 150 IU/kg | Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase GRASPA: Each patient will receive GRASPA at day 3 of the induction 1 phase. If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase | 3 | 14 | 13 | 14 | 14 | 14 |
| Escherichia sepsis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Aspergillosis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Pneumonia herpes viral | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Leukemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Tumor lysis syndrome | Metabolism and nutrition disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Antithrombin III decreased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Pancreatic enzymes increased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Arrythmia | Cardiac disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Cytolytic hepatitis | Hepatobiliary disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Metabolic encephalopathy | Nervous system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Bacterial Sepsis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Citrobacter infection | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Escherichia bacteraemia | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Klebsiella sepsis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Pneumocystitis jroveci infection | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Pseudomonal sepsis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Staphylococcal sepsis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Stenotrophomonas sepsis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Cerebrovascualr accident | Vascular disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Subarachnoid haemorrhage | Vascular disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Subclavian vein thrombosis | Vascular disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Venous thrombosis | Vascular disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Faecaloma | Gastrointestinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Haemmorhoids | Gastrointestinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Infusion site ulcer | General disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Multi-organ failure | General disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Blood fibrinogen decreased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Prothrombin level decreased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Pancreatic enzymes increased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Septic Shock | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Aspergillosis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Escherichia sepsis | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Leukemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Cytolytic hepatitis | Hepatobiliary disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Gastrointestinal disorders | Gastrointestinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Respiratory disorders | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| General disorder | General disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Nervous system | Nervous system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 (2011) | Systematic Assessment |
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| Vascular disorder | Vascular disorders | MedDRA 14.0 (2011) | Systematic Assessment |
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Not provided
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| Induction 1, Day 4 |
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| Induction 1, Day 10 |
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| Induction 1, Day 17 |
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| Induction 1, Day 22-28 |
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| Induction 2, Day 6 |
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| Induction 2, Day 7 |
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| Induction 2, Day 13 |
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| Induction 2, Day 20 |
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| Induction 2, Day 22 to D28 |
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| Induction 1, D4 |
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| Induction 1, D10 |
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| Induction 1, D17 |
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| Induction 1, D22-28 |
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| Induction 2, D6 |
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| Induction 2, D7 |
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| Induction 2, D13 |
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| Induction 2, D20 |
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| Induction 2, D22-28 |
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| Induction 1, D4 |
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| Induction 1, D10 |
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| Induction 1, D17 |
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| Induction 1, D22-28 |
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| Induction 2, D6 |
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| Induction 2, D7 |
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| Induction 2, D13 |
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| Induction 2, D20 |
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| Induction 2, D22-28 |
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| Induction 1, D4 |
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| Induction 1, D10 |
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| Induction 1, D17 |
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| Induction 1, D22-28 |
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| Induction 2, D6 |
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| Induction 2, D7 |
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| Induction 2, D13 |
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| Induction 2, D20 |
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| Induction 2, D22-28 |
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| Induction 1, D9 |
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| Induction 2, D2 |
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| Induction 2, D9 |
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| Induction 1, D9 |
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| Induction 2, D2 |
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| Induction 2, D9 |
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| Induction 1, D9 |
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| Induction 2, D2 |
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| Induction 2, D9 |
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| Induction 1, D9 |
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| Induction 2, D2 |
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| Induction 2, D9 |
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| Induction 1, D4 |
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| Induction 1, D10 |
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| Induction 1, D17 |
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| Induction 1, D22-28 |
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| Induction 2, D6 |
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| Induction 2, D7 |
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| Induction 2, D13 |
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| Induction 2, D20 |
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| Induction 2, D22-28 |
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| Induction 1, D4 |
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| Induction 1, D10 |
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| Induction 1, D17 |
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| Induction 1, D22-28 |
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| Induction 2, D6 |
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| Induction 2, D7 |
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| Induction 2, D13 |
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| Induction 2, D20 |
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| Induction 2, D22-28 |
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| Induction 1, D4 |
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| Induction 1, D22-28 |
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| Induction 2, D6 |
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| Induction 2, D22-28 |
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| Participants who met CR criteria at Induction 2 |
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