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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-006295-11 | EudraCT Number |
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Acute myeloid leukemia (AML) is a neoplasm of immature hematopoietic cells (blasts) with altered ripening capacity. Due to excessive proliferation, the blasts displace normal hematopoietic cells and bone marrow failure appears. Leukemic cells also infiltrate extramedullary tissues.
Following the standard chemotherapy treatment, the CR rate achieved is around 65-75% for all patients and 15% lower when considering only patients over 65 years. Modifications to the standard regimen consist of replacing the DNR for a cytotoxic one, modifying the dose of ara-C or adding a third drug.
Gemtuzumab ozogamicin (Mylotarg ®) is an immunoconjugate between anti-CD33 antibody and a cytotoxic antitumor antibiotic, calicheamicin. Mylotarg ® antibody specifically binds to CD33, a sialic acid-dependent adhesion protein expressed in over 90% of LMA10. Mylotarg ® selectively transports the cytotoxic agent calicheamicin into leukemic cells and hematopoietic progenitors differentiated from the myelomonocytic line, while respecting the pluripotent hematopoietic stem cells. Calicheamicin is released only after the fixation of the antibody anti-CD33 and its internalization by the cell, after which binds to and damages the DNA.
Mylotarg ® is approved in the U.S. for the treatment of CD33 positive AML in first relapse, for patients older than 60 years non-candidates for other intensive treatment modalities.
Since the efficacy of Mylotarg ® is equivalent and its toxicity profile less than the conventional therapy, it is logical to conduct a phase II trial exploring the role of Mylotarg ® in the early stages of treatment of AML.
Previous experience with gemtuzumab ozogamicin in relapsed patients led to its use combined with induction chemotherapy. The aim was to improve the CR rate reached with the latter and reduce relapse after achieving greater leukemic cytoreduction.
Recent data from the HOVON group support that the administration of G-CSF before and during induction chemotherapy decreases the incidence of relapse in patients with AML, particularly those considered to have intermediate risk.
Everything mentioned above justifies to investigate the combination of GO combined with chemotherapy with IDR and ara-C in standard 3x7 scheme and analyze the effect of sensitization with G-CSF in patients with AML de novo. If the treatment proposed here is effective and presents an acceptable toxicity it should be investigated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm, three cohorts | Experimental | Idarubicin, cytarabine, Mylotarg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mylotarg | Drug | Cohort 1 version 1.0. GO: 6mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV days 1 to 7, to begin 4 hours after the administration of GO. Cohort 1.0 version 2.0: GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV days 1 to 7, to begin 4 hours after the administration of GO. Cohort 2: G-CSF: 150 mcg/m^2, SC, days 0 to 7. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO. |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Remission of the Disease | Rate of patients that have obtained complete remission. Complete remission is defined as, bone marrow normocellular or slightly hypocellular with proportion of blasts <5%, including the erythroid cell count (and including promonocytes in case of M5), no Auer rods, no extramedullary leukemia, neutrophils and platelets rising. The persistence of minimal residual disease in immunophenotypic study will not invalidate the standard cytogenetic complete remission. | 28 days after chemotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary Toxicity to Mylotarg(R) | Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization | Baseline, weekly during treatment and at month 3 and month 6 after first induction. |
| Mortality at Induction |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jordi Sierra, MD | Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Germans Trias i Pujol | Badalona | Barcelona | 08916 | Spain | ||
| Hospital de la Santa Creu i Sant Pau |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 Version 1.0 | Mylotarg: Cohort 1 version 1.0 (5 evaluable patients): GO: 6 mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO. If chemo-sensitivity is observed after a first course of treatment (50% or more reduction of blasts compared to baseline) a second identical cycle will be administered. |
| FG001 | Cohort 1 Version 2.0 | Idarubicin, cytarabine, Mylotarg Mylotarg: Cohort 1 (20 evaluable patients): GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO. |
| FG002 | Cohort 2 | Cohort 2 (20 evaluable patients): G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
From cohort 1 version 1.0, one patient did not receive any study treatment (PIS withdrawal), for that reason is not considered for outcome assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1, Version 1.0 | Mylotarg: Cohort 1 version 1.0 (5 evaluable patients): GO: 6 mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO. If chemo-sensitivity is observed after a first course of treatment (50% or more reduction of blasts compared to baseline) a second identical cycle will be administered. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Complete Remission of the Disease | Rate of patients that have obtained complete remission. Complete remission is defined as, bone marrow normocellular or slightly hypocellular with proportion of blasts <5%, including the erythroid cell count (and including promonocytes in case of M5), no Auer rods, no extramedullary leukemia, neutrophils and platelets rising. The persistence of minimal residual disease in immunophenotypic study will not invalidate the standard cytogenetic complete remission. | Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible. | Posted | Count of Participants | Participants | 28 days after chemotherapy |
|
From October 2008 up to September 2016, 7 years and 11 months.
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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 | Cohort 1 | Idarubicin, cytarabine, Mylotarg, G-CSF. Mylotarg: Cohort 1 (20 evaluable patients): GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Transient Ischemic event | Nervous system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grade 4 hematologic toxicity | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jordi Sierra | CETLAM | +34 93 434 44 12 | jsierra@santpau.cat |
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| ID | Term |
|---|---|
| D000079982 | Gemtuzumab |
| ID | Term |
|---|---|
| D000080084 | Calicheamicins |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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|
all deaths occurring after the first administration of MylotargTM until the time of transplantation with no leukemic relapse has occurred, and all deaths in the 6 first months after administration of the second dose of MylotargTM with no leukemic relapse occurred. |
| Weekly during treatment, at third month and at 6 months after last administration of Mylotarg |
| Capacity to Obtain Hematopoietic Progenitor Cells (HPC) for Autotransplantation - DATA NOT COLLECTED | Rate of patients with capacity to obtain hematopoietic progenitor cells (HPC) for autotransplantation. This analysis has not been performed, because data were not available in sites. | One month before transplant, expected at 9 months after end of treatment. |
| Relapse After 6 Months | Rate of patients that have relapse after 6 months of obtained complete remission. | 6 months from complete remission |
| Survival After 6 Months | rate of patients alive within 6 months of obtained complete remission | 6 months after complete remission |
| Barcelona |
| 08025 |
| Spain |
| Hospital Clinic Barcelona | Barcelona | 08036 | Spain |
| Hospital Clinico Universitario de Salamanca | Salamanca | 37007 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Hospital ClÃnico Universitario de Valencia | Valencia | 496010 | Spain |
| BG001 | Cohort 1, Version 2.0 | Mylotarg: Cohort 1 (20 evaluable patients): GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO. |
| BG002 | Cohort 2 | Cohort 2 (20 evaluable patients): G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | The first 5 patients received GO 6mg/m2 but this dose was halted by unacceptable toxicity. Therefore, in Cohort 1 were included 20 patients receiving IA plus 3 mg/m2 GO. Cohort 2 included 20 patients who received treatment as in cohort 1 plus G-CSF priming | Count of Participants | Participants |
|
| Region of Enrollment | One patient has not been evaluated because has not received study treatment. | Number | participants |
|
| Leucocites at diagnosis | The first 5 patients received GO 6mg/m2 but this dose was halted by unacceptable toxicity. Therefore, in Cohort 1 were included 20 patients receiving IA plus 3 mg/m2 GO. Cohort 2 included 20 patients who received treatment as in cohort 1 plus G-CSF priming. | Median | Full Range | Cells x 10^9/L |
|
| Citogenetic | 1 patient not evaluable because has not received study treatment. | Count of Participants | Participants |
|
| OG001 | Cohort 1, Version 2.0 | Mylotarg: Cohort 1 (20 evaluable patients): GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO. |
| OG002 | Cohort 2 | Cohort 2 (20 evaluable patients): G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO. |
|
|
| Secondary | Secondary Toxicity to Mylotarg(R) | Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization | Posted | Number | percentage of participants | Baseline, weekly during treatment and at month 3 and month 6 after first induction. |
|
|
|
| Secondary | Mortality at Induction | all deaths occurring after the first administration of MylotargTM until the time of transplantation with no leukemic relapse has occurred, and all deaths in the 6 first months after administration of the second dose of MylotargTM with no leukemic relapse occurred. | Posted | Count of Participants | Participants | Weekly during treatment, at third month and at 6 months after last administration of Mylotarg |
|
|
|
| Secondary | Capacity to Obtain Hematopoietic Progenitor Cells (HPC) for Autotransplantation - DATA NOT COLLECTED | Rate of patients with capacity to obtain hematopoietic progenitor cells (HPC) for autotransplantation. This analysis has not been performed, because data were not available in sites. | Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible. This analysis has not been performed because data were not available for any of the cohorts studied. | Posted | One month before transplant, expected at 9 months after end of treatment. |
|
|
| Secondary | Relapse After 6 Months | Rate of patients that have relapse after 6 months of obtained complete remission. | Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible. | Posted | Number | percentage of participants | 6 months from complete remission |
|
|
|
| Secondary | Survival After 6 Months | rate of patients alive within 6 months of obtained complete remission | Initial 5 patients included in cohort 1 version 1.0 (closed due toxicity) have been evaluated for safety outcome but not evaluated for efficacy because the treatment is not feasible. | Posted | Number | percentage of participants | 6 months after complete remission |
|
|
|
| 1 |
| 20 |
| 3 |
| 20 |
| 20 |
| 20 |
| EG001 | Cohort 2 | Cohort 2 (20 evaluable patients): G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO. | 2 | 20 | 6 | 20 | 19 | 20 |
| EG002 | 5 Patients Treated in Trial With Prrotocol Version 1.0 | Idarubicin, cytarabine, Mylotarg, G-CSF. Mylotarg:: GO: 5 mg/m^2 (maximum 10 mg), IV infusion, 2 hours, day 1. If no adequate response, GO: 3 mg/m^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO. | 1 | 5 | 2 | 5 | 3 | 5 |
| Septic shock | Infections and infestations | Systematic Assessment |
|
| Severe respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Toxic megacolon | Infections and infestations | Systematic Assessment |
|
| Bilateral pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Febrile neutropenia | Infections and infestations | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Liver failure | Hepatobiliary disorders | Systematic Assessment |
|
| Hepatic Toxicity | Hepatobiliary disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Acute Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| G1/2 Hepatic toxicity | Hepatobiliary disorders | Systematic Assessment |
|
| G3/G4 Hepatic Toxicity | Hepatobiliary disorders | Systematic Assessment |
|
| Grade I/II infectous toxicity | Infections and infestations | Systematic Assessment |
|
| Grade 3 Infectous toxicity | Infections and infestations | Systematic Assessment |
|
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| D061067 |
| Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
|
| Grade I/II Hepatic toxicity |
|
| Grade III/IV hepatic toxicity |
|
| Grade I/II Infection |
|
| Grade III/IV Infection |
|