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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2018-00776 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 10000 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| RG9218023 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium |
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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
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This phase I/II trial studies the side effects and best dosing frequency of gemtuzumab ozogamicin when given in combination with granulocyte colony stimulating factor (G-CSF), cladribine, cytarabine and mitoxantrone (GCLAM) and to see how well they work in treating participants with acute myeloid leukemia or high-grade myeloid tumors (neoplasms) that have not been previously treated. Antibody-drug conjugates, such as gemtuzumab ozogamicin, act by directly delivering toxic chemotherapy to cancer cells. Granulocyte colony stimulating factor is a growth factor used to stimulate leukemia cells and render them more sensitive to chemotherapy drugs. Drugs used in chemotherapy, such as cladribine, cytarabine and mitoxantrone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gemtuzumab ozogamicin in combination with G-CSF, cladribine, cytarabine and mitoxantrone hydrochloride may work better in treating participants with acute myeloid leukemia or high-grade myeloid neoplasm.
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose (MTD) of gemtuzumab ozogamicin (GO) when added to GCLAM in patients with newly-diagnosed AML requiring induction chemotherapy. (Phase I) II. To evaluate the 6-month and 1-year event-free survival (EFS) rate with GO + GCLAM treated at the MTD. (Phase II)
SECONDARY OBJECTIVES:
I. Describe, within the limits of a phase 1/2 study, the toxicity profile of the study regimen.
II. Compare, within the limits of a phase 1/2 study, measurable residual disease (MRD) rates with GO + GCLAM at the MTD to patients treated previously with GCLAM alone.
III. Estimate, within the limits of a phase 1/2 study, the relationship between MRD status after induction therapy and relapse risk/time to relapse as well as relapse-free and overall survival.
IV. Compare, within the limits of a phase 1/2 study, complete remission rates with GO + GCLAM at the MTD to patients treated previously with GCLAM alone.
V. Compare, within the limits of a phase 1/2 study, overall survival rates with GO + GCLAM at the MTD to patients treated previously with GCLAM alone VI. Evaluate, within the limits of a phase 1/2 study, the impact of GO dosing regimens on the duration of cytopenias.
VII. Collect biological specimens for use for the future laboratory investigation of biomarkers for response to GO.
OUTLINE: This is a phase I dose escalation study of gemtuzumab ozogamicin followed by a phase II study.
INDUCTION THERAPY: Participants receive gemtuzumab ozogamicin intravenously (IV) either as a single dose on day 1, or as three doses on days 1, 4, and 7. Participants also receive G-CSF subcutaneously (SC) on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, and mitoxantrone hydrochloride IV on days 1-3. Patients who do not achieve a CR or CRi following the first cycle of induction are eligible for a second cycle, which is given without gemtuzumab ozogamicin. Participants with a complete remission (CR) or complete remission with incomplete count recovery (CRi) may then proceed to Post-Remission Therapy.
POST-REMISSION THERAPY: Participants receive G-CSF, cladribine, and cytarabine as in Induction Therapy during cycle 1, and cytarabine IV every 12 hours on days 1-6 of cycles 2-3. Treatment repeats every month for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up every 3 months for 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (GO, GCLAM) | Experimental | INDUCTION THERAPY: Participants receive gemtuzumab ozogamicin IV either as a single dose on day 1, or as three doses on days 1, 4, and 7. Participants also receive G-CSF SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, and mitoxantrone hydrochloride IV on days 1-3. Patients who do not achieve a CR or CRi following the first cycle of induction are eligible for a second cycle, which is given without gemtuzumab ozogamicin. Participants with a CR or CRi may then proceed to Post-Remission Therapy. POST-REMISSION THERAPY: Participants receive G-CSF, cladribine, and cytarabine as in Induction Therapy during cycle 1, and cytarabine IV every 12 hours on days 1-6 of cycles 2-3. Treatment repeats every month for up to 3 cycles in the absence of disease progression or unacceptable toxicity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cladribine | Drug | Given IV |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Gemtuzumab Ozogamicin (GO) When Added to GCLAM (Phase 1) | Defined as the highest dose studied in which the incidence of Dose Limiting Toxicity (DLT) is ≤33% (≤4 of 12 patients experiencing DLT), defined as any Grade 3 non-hematologic toxicity lasting >48 hours that results in >7-day delay of the subsequent treatment cycle, with the exception of febrile neutropenia or infection or toxicities secondary to febrile neutropenia or infection, or any Grade ≥4 non-hematologic toxicity except febrile neutropenia/infection (or toxicities secondary to febrile neutropenia or infection) unless felt to be a direct consequence of treatment-related toxicity (e.g. intestinal infection following mucosal barrier breakdown), and with the exception of constitutional symptoms if recovery to Grade ≤2 within 14 days. The National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 will be used. | At time of count recovery, second cycle of treatment, response assessment or removal from protocol (at approximately 1 month). |
| Event-free Survival (EFS) Rate (Phase 2) | A two-stage design will be used to evaluate the EFS. Patients treated at the maximum tolerated dose (MTD) from the phase 1 portion of the trial will be used in the phase 2 analysis. If censoring occurs, secondary analyses analyzing 6-month or 1-year EFS accounting for censoring will be done, including estimating 6-month or 1-year EFS using the Kaplan-Meier method. The first stage of the two-stage phase 2 design will evaluate 30 patients. If 20 or more of the first 30 patients are alive without event at 6-months after study registration, an additional 30 patients will be enrolled. If 46 or more of the 60 patients treated at the MTD are alive and without event at 6-months after study registration, the study will consider the regimen of interest for further investigation. Patients last known to be alive in CR were censored at date of last contact. | From the start of study treatment, assessed at 6 months and 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| 30-day All-cause Mortality | As a summary of adverse events (captured on trial using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), 30-day all cause mortality is reported as a percent of patients treated at the MTD/RP2D. Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roland Walter | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | GO1 Dose Level Phase 1 | Participants received 1 dose of gemtuzumab ozogamicin (GO) intravenously at 3 mg/m2 per dose on day 1. All doses of GO were capped at 4.5 mg. |
| FG001 | GO3 Dose Level Includes Phase 1 and Phase 2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 17, 2022 |
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| Cytarabine | Drug | Given IV |
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| Gemtuzumab Ozogamicin | Drug | Given IV |
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| Recombinant Granulocyte Colony-Stimulating Factor | Biological | Given SC |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
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| Mitoxantrone Hydrochloride | Drug | Given IV |
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| Up to 5 years. 30-day all-cause mortality is reported |
| Relapse-free Survival of GO3 Cohort | RFS was calculated for participants who achieved a complete remission (with or without count recovery; CR or CRi) and measured from the date remission to the first of relapse from CR/CRi or death from any cause. Patients last known to be alive in CR /CRi were censored at date of last contact. Will be estimated using the Kaplan-Meier method. Time to relapse will be estimated using non-parametric estimates of the cumulative incidence curve with death analyzed as a competing event. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. | Up to 5 years. 2-year RFS reported. |
| Overall Survival | OS was calculated for all participants and measured from initial trial therapy to death from any cause. Patients last known ot be alive were censored at date of last contact. Will be estimated using the Kaplan-Meier method. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. | 3 years and 1 month |
| Measurable Residual Disease (MRD) Rates and Remission Rates: CR | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. Complete response (CR) rate is defined as the frequency of patients achieving CR, which is defined by the European LeukemiaNet 2017 guidelines as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 x 109/L (1000/mL); platelet count ≥100 x 109/L. (100 000/mL). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance tests were not performed. | 90 days |
| Measurable Residual Disease (MRD) and Remission Rates: CRi (MRDneg) | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. Complete response with incomplete hematologic recovery (CRi) rate is defined as the frequency of patients achieving CRi, which is defined by the European LeukemiaNet 2017 guidelines as all CR criteria except for residual neutropenia (ANC <1.0 x 109/L [1000/mL]) or thrombocytopenia (platelet count <100 x 109/L [100,000/mL]). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance tests were not performed. | 90 days |
| Measurable Residual Disease (MRD) and Remission Rates: CR/CRi | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. Complete response (CR) + complete response with incomplete hematologic recovery (CRi) rate is defined as the frequency of patients achieving CR or CRi per the European LeukemiaNet 2017 criteria as defined above. MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance tests were not performed. | 90 days |
| Measurable Residual Disease (MRD) and Remission Rates: MLFS (MRDneg) | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. Morphologic leukemia free state (MLFS) rate is defined as the frequency of patients achieving MLFS, which is defined by the European LeukemiaNet guidelines as bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. At least 200 cells should be enumerated or cellularity should be at least 10%. MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance | 90 days |
| Measurable Residual Disease (MRD) and Remission Rates: Alapasia (MRDneg) | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. o Aplasia rate is defined in this protocol as frequency of patients without blood count recovery after chemotherapy and bone marrow examination showing hypocellularity not meeting cellularity criteria for morphologic leukemia free state (MLFS). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance tests were not performed. | 90 days |
Phase 1: Participants received 3 doses of gemtuzumab ozogamicin (GO) intravenously at 3 mg/m2 per dose on days 1, 4, and 7.
Phase 2: Participants received CLAG-M(cladribine, high-dose cytarabine, G-CSF and dose-escalated mitoxantrone)/GO at the recommended phase 2 dose (RP2D) identified in phase 1.
All doses of GO were capped at 4.5 mg.
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | GO1 Dose Level Phase 1 | Participants received 1 dose of gemtuzumab ozogamicin (GO) intravenously at 3 mg/m2 per dose on day 1. All doses of GO were capped at 4.5 mg. |
| BG001 | GO3 Dose Level Includes Phase 1 and Phase 2 | Phase 1: Participants received 3 doses of gemtuzumab ozogamicin (GO) intravenously at 3 mg/m2 per dose on days 1, 4, and 7. Phase 2: Participants received CLAG-M(cladribine, high-dose cytarabine, G-CSF and dose-escalated mitoxantrone)/GO at the recommended phase 2 dose (RP2D) identified in phase 1. All doses of GO were capped at 4.5 mg. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 | |||||||||||||||||||||||
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| Primary | Maximum Tolerated Dose (MTD) of Gemtuzumab Ozogamicin (GO) When Added to GCLAM (Phase 1) | Defined as the highest dose studied in which the incidence of Dose Limiting Toxicity (DLT) is ≤33% (≤4 of 12 patients experiencing DLT), defined as any Grade 3 non-hematologic toxicity lasting >48 hours that results in >7-day delay of the subsequent treatment cycle, with the exception of febrile neutropenia or infection or toxicities secondary to febrile neutropenia or infection, or any Grade ≥4 non-hematologic toxicity except febrile neutropenia/infection (or toxicities secondary to febrile neutropenia or infection) unless felt to be a direct consequence of treatment-related toxicity (e.g. intestinal infection following mucosal barrier breakdown), and with the exception of constitutional symptoms if recovery to Grade ≤2 within 14 days. The National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 will be used. | Posted | Count of Participants | Participants | At time of count recovery, second cycle of treatment, response assessment or removal from protocol (at approximately 1 month). |
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| Primary | Event-free Survival (EFS) Rate (Phase 2) | A two-stage design will be used to evaluate the EFS. Patients treated at the maximum tolerated dose (MTD) from the phase 1 portion of the trial will be used in the phase 2 analysis. If censoring occurs, secondary analyses analyzing 6-month or 1-year EFS accounting for censoring will be done, including estimating 6-month or 1-year EFS using the Kaplan-Meier method. The first stage of the two-stage phase 2 design will evaluate 30 patients. If 20 or more of the first 30 patients are alive without event at 6-months after study registration, an additional 30 patients will be enrolled. If 46 or more of the 60 patients treated at the MTD are alive and without event at 6-months after study registration, the study will consider the regimen of interest for further investigation. Patients last known to be alive in CR were censored at date of last contact. | GO1 participants were treated in dose escalation. The primary endpoint per protocol is to assess the EFS rate at the MTD or RP2D and was not assessed at dose levels below the RP2D. | Posted | Number | 95% Confidence Interval | percent of participants | From the start of study treatment, assessed at 6 months and 1 year |
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| Secondary | 30-day All-cause Mortality | As a summary of adverse events (captured on trial using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), 30-day all cause mortality is reported as a percent of patients treated at the MTD/RP2D. Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. | 30-day mortality is reported among patients treated at the MTD/RP2D. There is no study-related reason to report survival data on the GO1 dose level. No efficacy assessments were evaluated during the GO1 phase 1 dose escalation study which focuses on DLT/toxicity assessments. | Posted | Number | 95% Confidence Interval | proportion died on/before day 30 | Up to 5 years. 30-day all-cause mortality is reported |
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| Secondary | Relapse-free Survival of GO3 Cohort | RFS was calculated for participants who achieved a complete remission (with or without count recovery; CR or CRi) and measured from the date remission to the first of relapse from CR/CRi or death from any cause. Patients last known to be alive in CR /CRi were censored at date of last contact. Will be estimated using the Kaplan-Meier method. Time to relapse will be estimated using non-parametric estimates of the cumulative incidence curve with death analyzed as a competing event. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. | RFS is reported among patients treated at the MTD/RP2D. There is no study-related reason to report survival data on the GO1 dose level. No efficacy assessments were evaluated during the GO 1 phase 1 dose escalation study which focuses on DLT/toxicity assessments. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 5 years. 2-year RFS reported. |
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| Secondary | Overall Survival | OS was calculated for all participants and measured from initial trial therapy to death from any cause. Patients last known ot be alive were censored at date of last contact. Will be estimated using the Kaplan-Meier method. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. | RFS is reported among patients treated at the MTD/RP2D. There is no study-related reason to report survival data on the GO1 dose level. No efficacy assessments were evaluated during the GO1 phase 1 dose escalation study which focuses on DLT/toxicity assessments. | Posted | Number | 95% Confidence Interval | percentage of participants | 3 years and 1 month |
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| Secondary | Measurable Residual Disease (MRD) Rates and Remission Rates: CR | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. Complete response (CR) rate is defined as the frequency of patients achieving CR, which is defined by the European LeukemiaNet 2017 guidelines as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 x 109/L (1000/mL); platelet count ≥100 x 109/L. (100 000/mL). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance tests were not performed. | Posted | Count of Participants | Participants | 90 days |
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| Secondary | Measurable Residual Disease (MRD) and Remission Rates: CRi (MRDneg) | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. Complete response with incomplete hematologic recovery (CRi) rate is defined as the frequency of patients achieving CRi, which is defined by the European LeukemiaNet 2017 guidelines as all CR criteria except for residual neutropenia (ANC <1.0 x 109/L [1000/mL]) or thrombocytopenia (platelet count <100 x 109/L [100,000/mL]). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance tests were not performed. | Posted | Count of Participants | Participants | 90 days |
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| Secondary | Measurable Residual Disease (MRD) and Remission Rates: CR/CRi | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. Complete response (CR) + complete response with incomplete hematologic recovery (CRi) rate is defined as the frequency of patients achieving CR or CRi per the European LeukemiaNet 2017 criteria as defined above. MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance tests were not performed. | GO1: remission rates for 6 patients: CR rate was 4/6, CR+CRi rate was 5/6 (all MRDneg) | Posted | Count of Participants | Participants | 90 days |
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| Secondary | Measurable Residual Disease (MRD) and Remission Rates: MLFS (MRDneg) | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. Morphologic leukemia free state (MLFS) rate is defined as the frequency of patients achieving MLFS, which is defined by the European LeukemiaNet guidelines as bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. At least 200 cells should be enumerated or cellularity should be at least 10%. MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance | Posted | Count of Participants | Participants | 90 days |
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| Secondary | Measurable Residual Disease (MRD) and Remission Rates: Alapasia (MRDneg) | Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. o Aplasia rate is defined in this protocol as frequency of patients without blood count recovery after chemotherapy and bone marrow examination showing hypocellularity not meeting cellularity criteria for morphologic leukemia free state (MLFS). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry. Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS. Statistical significance tests were not performed. | Posted | Count of Participants | Participants | 90 days |
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Serious adverse events and other (not including serious) adverse events were monitored and recorded for only the first cycle of therapy (the only period of experimental therapy). Patients were monitored from the start of the first drug administration (on day 0 or day 1) until the start of the second cycle of therapy, or until 1 month post the first response assessment. All-Cause Mortality was assessed for 3 years and 1 month.
Adverse events were collected systematically through regular investigator and study staff assessment in combination with reviews of clinical, laboratory, and imaging records and ongoing direct communication with treating physicians and sub-investigators. Only adverse events rated grade 3 or higher, with the exception of all hematologic toxicities, are recorded, graded, and reported. Grading drawn from CTCAE version 5.0.
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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 | GO1 Dose Level Phase 1 | Participants received 1 dose of gemtuzumab ozogamicin (GO) intravenously at 3 mg/m2 per dose on day 1. All doses of GO were capped at 4.5 mg. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG001 | GO3 Dose Level Includes Phase 1 and Phase 2 | Phase 1: Participants received 3 doses of gemtuzumab ozogamicin (GO) intravenously at 3 mg/m2 per dose on days 1, 4, and 7. Phase 2: Participants received CLAG-M(cladribine, high-dose cytarabine, G-CSF and dose-escalated mitoxantrone)/GO at the recommended phase 2 dose (RP2D) identified in phase 1. All doses of GO were capped at 4.5 mg. | 2 | 60 | 10 | 60 | 59 | 60 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grade 4 Bronchopulmonary Hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 3 Left Ventricular Systolic Dysfunction | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 4 Aspartate Aminotransferase Increase | Investigations | CTCAE (5.0) | Systematic Assessment |
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| Grade 3 Reversible Posterior Leukoencephalopathy Syndrome | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 3 Intercranial Hemorrhage | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 3 Ataxia | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 4 Tumor Lysis | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 3 Pericardial Effusion | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 3 Hip Fracture | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment |
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| Grade 4 Upper Gastrointestinal Hemorrhage | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 3 Encephalitis Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
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| Grade 3 Stroke | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
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| Grade 4 Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 4 Respiratory Failure | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 4 Cardiac Arrest | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grade 3 Febrile Neutropenia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Esophageal Hemorrhage | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Bacteremia | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Enterocolitis | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Chest Pain - Cardiac | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Sepsis | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 4 Sepsis | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hypotension | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hypertension | Vascular disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Skin Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Headache | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Lung Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Perineal Pain | Reproductive system and breast disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Vaginal Hemorrhage | Reproductive system and breast disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Alanine Aminotransferase Increase | Investigations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hypokalemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 4 Hypokalemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Tumor Lysis Syndrome | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Upper Gastrointestinal Hemorrhage | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Lower Gastrointestinal Hemorrhage | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Disseminated Intravascular Coagulation | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Urinary Tract Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Intracranial Hemorrhage | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Aspartate Aminotransferase Increase | Investigations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hepatic Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Typhlitis | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Left Ventricular Systolic Dysfunction | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Ejection Fraction Decrease | Investigations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Vomiting | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Atrial Fibrillation | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Myocardial Infarction | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Acute Kidney Injury | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 4 Acute Kidney Injury | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hematuria | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hyperglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Dysarthria | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Esophagitis | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Mucositis Oral | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hypocalcemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 4 Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hyperphosphatemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Constipation | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Heart Failure | Cardiac disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Syncope | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Generalized Edema | General disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Catheter Related Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Rash Maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Dysphagia | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Acidosis | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Encephalopathy | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hypernatremia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 4 Hypernatremia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Anorexia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Shingles | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Bronchopulmonary Hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Dental Caries | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Colonic Perforation | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Colonic Hemorrhage | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Anorectal Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Menorrhagia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Grade 3 Arthritis | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
|
This is a single center study and generalizability to other centers is unclear. This is a non-randomized, single arm study without a contemporaneously enrolled control arm. The number of participants at the phase 1 dose level GO1 was insufficient to perform statistically reliable analyses.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Roland Walter, Member of Clinical Research Division | Fred Hutchinson Cancer Center | 206-667-3599 | rwalter@fredhutch.org |
| Jul 27, 2022 |
| Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 10, 2019 | Jul 27, 2022 | ICF_003.pdf |
Not provided
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D017338 | Cladribine |
| D003561 | Cytarabine |
| D000079982 | Gemtuzumab |
| C423652 | pegylated granulocyte colony-stimulating factor |
| D008942 | Mitoxantrone |
| ID | Term |
|---|---|
| D015762 | 2-Chloroadenosine |
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003839 | Deoxyadenosines |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001087 | Arabinonucleosides |
| D000080084 | Calicheamicins |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| 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 |
| D000880 | Anthraquinones |
| D000095322 | Anthrones |
| D000873 | Anthracenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011809 | Quinones |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| >=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 |
|
|
|
|
|
Phase 1: Participants received 3 doses of gemtuzumab ozogamicin (GO) intravenously at 3 mg/m2 per dose on days 1, 4, and 7.
Phase 2: Participants received CLAG-M(cladribine, high-dose cytarabine, G-CSF and dose-escalated mitoxantrone)/GO at the recommended phase 2 dose (RP2D) identified in phase 1.
All doses of GO were capped at 4.5 mg.
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