A Phase 2 interventional study of Mylotarg in Novo Acute Myeloid Leukemia, sponsored by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias. Completed at 6 sites in Spain. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2021-01-27.
Sponsored by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias · Phase 2, Interventional, and Treatment
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.
5,442 studies on the registry are indexed under Leukemia; 637 are open to participants now.
This study's enrollment of 46 is above the median of 38 across 4,248 interventional studies indexed under Leukemia.
Browse Leukemia studies →Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias is the lead sponsor of 7 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Idarubicin, cytarabine, Mylotarg.
Drug: Mylotarg
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.
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.
Time frame: 28 days after chemotherapy
Secondary Toxicity to Mylotarg(R)
Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization
Time frame: Baseline, weekly during treatment and at month 3 and month 6 after first induction.
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.
Time frame: 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.
Time frame: 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.
Time frame: 6 months from complete remission
Survival After 6 Months
rate of patients alive within 6 months of obtained complete remission
Time frame: 6 months after complete remission
| Milestone | Cohort 1 Version 1.0 | Cohort 1 Version 2.0 | Cohort 2 |
|---|---|---|---|
| Started | 6 | 20 | 20 |
| Completed | 5 | 20 | 20 |
| Not completed | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 |
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.
| Participants | Cohort 1, Version 1.0 | Cohort 1, Version 2.0 | Cohort 2 |
|---|---|---|---|
| Complete Response | NA | 18 | 16 |
| Partial Response | NA | 1 | 2 |
| Refractory | NA | 1 | 2 |
Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization
| percentage of participants | Cohort 1, Version 1.0 | Cohort 1, Version 2.0 | Cohort 2 |
|---|---|---|---|
| Grade IV Hematologic toxicity | 0 | 100 | 95 |
| Grade II Hematologic toxicity | 0 | 0 | 5 |
| Grade I/II Hepatic toxicity | 20 | 10 | 10 |
| Grade III/IV hepatic toxicity | 40 | 5 | 15 |
| Grade I/II Infection | 0 | 10 | 25 |
| Grade III/IV Infection | 0 | 5 | 30 |
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.
| Participants | Cohort 1, Version 1.0 | Cohort 1 Version 2.0 | Cohort 2 |
|---|---|---|---|
| Mortality at Induction | 1 | 0 | 2 |
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.
No measurements were reported for this outcome.
Rate of patients that have relapse after 6 months of obtained complete remission.
| percentage of participants | Cohort 1, Version 2.0 | Cohort 2 |
|---|---|---|
| Relapse After 6 Months | 30 | 59 |
rate of patients alive within 6 months of obtained complete remission
| percentage of participants | Cohort 1 | Cohort 2 |
|---|---|---|
| Survival After 6 Months | 80 | 80 |
Collected over From October 2008 up to September 2016, 7 years and 11 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1 | 1/20 (5%) | 3/20 (15%) | 20/20 (100%) |
| Cohort 2 | 2/20 (10%) | 6/20 (30%) | 19/20 (95%) |
| 5 Patients Treated in Trial With Prrotocol Version 1.0 | 1/5 (20%) | 2/5 (40%) | 3/5 (60%) |
| Event | Cohort 1 | Cohort 2 | 5 Patients Treated in Trial With Prrotocol Version 1.0 |
|---|---|---|---|
| Hepatic ToxicityHepatobiliary disorders | 0/20 | 0/20 | 2/5 |
| Severe respiratory failureRespiratory, thoracic and mediastinal disorders | 0/20 | 2/20 | 0/5 |
| Febrile neutropeniaInfections and infestations | 1/20 | 2/20 | 0/5 |
| Transient Ischemic eventNervous system disorders | 0/20 | 1/20 | 0/5 |
| Septic shockInfections and infestations | 0/20 | 1/20 | 0/5 |
| Toxic megacolonInfections and infestations | 0/20 | 1/20 | 0/5 |
| Bilateral pneumoniaRespiratory, thoracic and mediastinal disorders | 1/20 | 0/20 | 0/5 |
| AnemiaBlood and lymphatic system disorders | 1/20 | 0/20 | 0/5 |
| Liver failureHepatobiliary disorders | 0/20 | 1/20 | 0/5 |
| NeutropeniaBlood and lymphatic system disorders | 1/20 | 0/20 | 0/5 |
| Event | Cohort 1 | Cohort 2 | 5 Patients Treated in Trial With Prrotocol Version 1.0 |
|---|---|---|---|
| Grade 4 hematologic toxicityBlood and lymphatic system disorders | 20/20 | 19/20 | 3/5 |
| Grade 3 Infectous toxicityInfections and infestations | 1/20 | 6/20 | 0/5 |
| Grade I/II infectous toxicityInfections and infestations | 2/20 | 5/20 | 0/5 |
| G3/G4 Hepatic ToxicityHepatobiliary disorders | 1/20 | 3/20 | 0/5 |
| G1/2 Hepatic toxicityHepatobiliary disorders | 2/20 | 2/20 | 0/5 |
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.
| Age, Continuous(years) | Cohort 1, Version 1.0 | Cohort 1, Version 2.0 | Cohort 2 | Total |
|---|---|---|---|---|
| Median | 56 (32 to 61) | 49 (22 to 64) | 61 (24 to 69) | 61 (22 to 69) |
| Sex: Female, Male(Participants) | Cohort 1, Version 1.0 | Cohort 1, Version 2.0 | Cohort 2 | Total |
|---|---|---|---|---|
| Female | 2 | 9 | 5 | 16 |
| Male | 3 | 11 | 15 | 29 |
| Region of Enrollment(participants) | Cohort 1, Version 1.0 | Cohort 1, Version 2.0 | Cohort 2 | Total |
|---|---|---|---|---|
| Spain | 5 | 20 | 20 | 45 |
| Leucocites at diagnosis(Cells x 10^9/L) | Cohort 1, Version 1.0 | Cohort 1, Version 2.0 | Cohort 2 | Total |
|---|---|---|---|---|
| Median | 13.48 (2.1 to 31.85) | 7.66 (1 to 96.6) | 6.96 (0.9 to 114) | 6.96 (0.9 to 114) |
| Citogenetic(Participants) | Cohort 1, Version 1.0 | Cohort 1, Version 2.0 | Cohort 2 | Total |
|---|---|---|---|---|
| Favorable | 1 | 5 | 3 | 9 |
| Intermediate | 3 | 13 | 12 | 28 |
| Adverse | 1 | 2 | 5 | 8 |
This study is completed, as verified in Jan 2021. You cannot join it, but the record below documents what was studied.
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