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This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects.
The Phase II portion of this study is to see what side effects are seen with medication after transplant.
Inotuzumab ozogamicin is a combination of an antibody and chemotherapy which has been shown to have significant activity against relapsed/refractory acute lymphocytic leukemia (ALL).
Inotuzumab ozogamicin is considered experimental in this study.
Study Design This is a Phase I/II study of inotuzumab ozogamicin for the treatment of patients who underwent allogeneic transplantation for ALL and have a high risk of relapse. The Phase I portion of this study will be a 3+3 dose escalation trial. This is followed by a phase 2 cohort at the recommended Phase 2 dose (RP2D). Participants will receive study treatment up to 4 cycles until relapse of disease, unacceptable toxicity, or death, whichever occurs first
Phase I: Inotuzumab Ozogamicin Dosing Escalation Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach.
Phase II: Inotuzumab Ozogamicin Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach. In order to be included in the safety profile endpoint review, subjects must have received at least of 1 cycle of treatment.
Primary Objective
Phase I: To define a post hematopoietic stem cell transplantation maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of inotuzumab ozogamicin.
Phase II: To assess the efficacy of inotuzumab ozogamicin as measured by diseasefree survival (DFS) at one year.
Secondary Objective(s)
Phase I:
Phase II:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inotuzumab Ozogamicin | Experimental | Phase I: A maximum of 4 cycles will be allowed and doses will be adjusted in 0.1mg/m2 increments using a dose escalation scale depending on tolerability. Total range of dose levels for participants is 0.1-0.6mg/m^2. Phase II: Participants will be enrolled until all Phase I participants have been followed and assessed for toxicity for at least 4 weeks after the fourth treatment dose of inotuzumab ozogamicin or 4 weeks after the participant goes off treatment, whichever comes first. Doses to be administered will be determined in the phase I portion of the study. The recommended phase 2 dose is 0.3mg/m2. Repeat cycles every 28 days for up to 4 cycles |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inotuzumab Ozogamicin | Drug | Inotuzumab ozogamicin, IV, 28 day cycles Phase 1 dosages: Dose Level -2 (0.1 mg/m^2) Dose Level -1 (0.2 mg/m^2) Dose Level 0 (0.3 mg/m^2) Dose Level 1 (0.4 mg/m^2) Dose Level 2 (0.5 mg/m^2) Dose Level 3 (0.6 mg/m^2) |
| Measure | Description | Time Frame |
|---|---|---|
| Phase I MTD | Defined post hematopoietic stem cell transplantation MTD | Up to 112 days (16 weeks) |
| Phase I DLTs | Frequency of DLTs during the first two cycles in ALL-participants | Up to 112 days (16 weeks) |
| Phase II Median DFS | Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested | At 3 months after initial treatment |
| Phase II Median DFS | Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested | At 6 months after initial treatment |
| Phase II Median DFS | Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested |
| Measure | Description | Time Frame |
|---|---|---|
| Phase I Median DFS | Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)" Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 |
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Inclusion Criteria:
Phase 1 Inclusion Criteria
Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
Patients who are between T+40 and T+100 after allogeneic transplantation. Patients must receive their first dose of inotuzumab at or before T+100.
Patients who have/are either:
Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation
---Pre- or Post-Transplant Minimal Residual Disease defined by:
----Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication.
In second or third complete remission at the time of allogeneic transplantation
Treated with reduced intensity regimens or non-myeloablative conditioning regimens
Lymphoid blast crisis of CML
Are relapsed or refractory to at least 1 line of chemotherapy
Philadelphia-like ALL
Patients who have evidence of donor chimerism after allogeneic transplantation.
ECOG Performance status < 2
Participants must have ANC > 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/µL for 7 days.
Able to adhere to the study visit schedule and other protocol requirements.
Participants must have the ability to understand and the willingness to sign a written informed consent document.
Phase 2 Inclusion Criteria
Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
Patients who are between T+40 and T+100 after allogeneic transplantation
Patients who have/are either:
Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation
---Post-Transplant Minimal Residual Disease defined by:
----Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication.
In second or third complete remission at the time of allogeneic transplantation
Treated with reduced intensity regimens as defined per institutional standard of practice
Lymphoid blast crisis of CML
Are relapsed or refractory to at least 1 line of chemotherapy
Philadelphia-like ALL
Patients who have > 80% donor chimerism after allogeneic transplantation.
Philadelphia chromosome positive ALL must have failed at least 1 TKI
ECOG Performance status < 1
pre-transplant evaluation, see 10.1.1
Participants must have ANC > 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/µL for 7 days.
Able to adhere to the study visit schedule and other protocol requirements.
Participants must have the ability to understand and the willingness to sign a written informed consent document.
Phase 1 and 2 Exclusion Criteria:
Patients with clinical evidence of disease progression prior to enrollment
Persistent prior treatment toxicities Grade 2 and above according to NCI CTCAE Version 4.03 (with the exception for alopecia, neuropathy, etc.)
Patients with inadequate organ function as defined by:
GVHD grade III or IV (for patients with a prior allogeneic transplant).
Active acute or chronic GVHD of the liver (for patients with a prior allogeneic transplant)
History of VOD
Use of concomitant TKI or sirolimus
Second active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast)
Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant or breastfeeding women are excluded from this study because inotuzumab ozogamicin may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with inotuzumab ozogamicin, breastfeeding should be discontinued if the mother is treated with inotuzumab ozogamicin. These potential risks may also apply to other agents used in this study.
Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
Participation in any other investigational drug study or had exposure to any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Leland Metheny, MD | Contact | 1-800-641-2422 | CTUReferral@UHhospitals.org | |
| Ron Sobecks, MD | Contact | 216-444-6833 | sobeckr@ccf.org |
| Name | Affiliation | Role |
|---|---|---|
| Leland Metheny, MD | University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Kansas Cancer Center | Recruiting | Westwood | Kansas | 66205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41671463 | Derived | Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067. | |
| 38170741 | Derived | Metheny LL, Sobecks R, Cho C, Fu P, Margevicius S, Wang J, Ciarrone L, Kopp S, Convents RD, Majhail N, Caimi PF, Otegbeye F, Cooper BW, Gallogly M, Malek E, Tomlinson B, Gerds AT, Hamilton B, Giralt S, Perales MA, de Lima M. A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia. Blood Adv. 2024 Mar 26;8(6):1384-1391. doi: 10.1182/bloodadvances.2023011514. |
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| 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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| ID | Term |
|---|---|
| D000080045 | Inotuzumab Ozogamicin |
| ID | Term |
|---|---|
| D000080084 | Calicheamicins |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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| At 9 months after initial treatment |
| Phase II Median DFS | Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested | At 1 year after initial treatment |
| Phase II Median DFS | Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested | Post first dose of inotuzumab ozogamicin |
| At 3 months after initial treatment |
| Phase I Median DFS | Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)" Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 6 months after initial treatment |
| Phase I Median DFS | Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)" Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 9 months after initial treatment |
| Phase I Median DFS | Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)" Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 1 year after initial treatment |
| Phase I Median DFS | Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)" Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days |
| Phase I NRM | Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR). Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 3 months after initial treatment |
| Phase I NRM | Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR). Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 6 months after initial treatment |
| Phase I NRM | Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR). Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 9 months after initial treatment |
| Phase I NRM | Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR). Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 1 year after initial treatment |
| Phase I NRM | Phase I NRM , defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR). Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days |
| Phase I Relapse | Phase I relapse rate, defined as time from date of first dose to the date of first relapse. Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 3 months after initial treatment |
| Phase I Relapse | Phase I relapse rate, defined as time from date of first dose to the date of first relapse. Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 6 months after initial treatment |
| Phase I Relapse | Phase I relapse rate, defined as time from date of first dose to the date of first relapse. Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 9 months after initial treatment |
| Phase I Relapse | Phase I relapse rate, defined as time from date of first dose to the date of first relapse. Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 1 year after initial treatment |
| Phase I Relapse | Phase I relapse rate, defined as time from date of first dose to the date of first relapse. Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days |
| Phase I Relapse-related mortality | Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 3 months after initial treatment |
| Phase I Relapse-related mortality | Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 6 months after initial treatment |
| Phase I Relapse-related mortality | Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 9 months after initial treatment |
| Phase I Relapse-related mortality | Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 1 year after initial treatment |
| Phase I Relapse-related mortality | Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days |
| Phase I Median OS | Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 3 months after initial treatment |
| Phase I Median OS | Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 6 months after initial treatment |
| Phase I Median OS | Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 9 months after initial treatment |
| Phase I Median OS | Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 1 year after initial treatment |
| Phase I Median OS | Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days |
| Phase I Incidence of myeloid toxicity | Number of patients who develop myeloid toxicity while on study, defined as grade of anemia, neutropenia and thrombocytopenia CTCAE 4 | At 1 year |
| Phase I Incidence of secondary graft failure | Number of patients who develop secondary graft failure while on study, defined as: Either cytopenias after initial engraftment (ANC <500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was >5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced | At 1 year |
| Phase I incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) | Safety profile of intervention as measured by incidence of VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:
| At 1 year |
| Phase I rate of VOD/SOS - number of participants affected | Safety profile of intervention as measured by number of participants affected by VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:
| At 1 year |
| Phase I - Percent of participants with grade 3 + AE/SAEs | Phase I safety profile of intervention as measured by percent of participants with grade 3 + AE/SAEs | At 1 year |
| Phase II Non-relapse mortality (NRM) | Phase II Non-relapse mortality (NRM), defined as time from date of first dose to death due to any cause without prior relapse. Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 3 months after initial treatment |
| Phase II Relapse | Phase II relapse rate, defined as time from date of first dose to the date of first relapse. Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 6 months after initial treatment |
| Phase II Relapse | Phase II relapse rate, defined as time from date of first dose to the date of first relapse. Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 9 months after initial treatment |
| Phase II Relapse-related mortality | Phase II Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | At 1 year after initial treatment |
| Phase II Relapse-related mortality | Phase II Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI | Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days |
| Phase II Median OS | Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 3 months after initial treatment |
| Phase II Median OS | Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 6 months after initial treatment |
| Phase II Median OS | Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 9 months after initial treatment |
| Phase II Median OS | Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | At 1 year after initial treatment |
| Phase II Median OS | Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 | Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days |
| Phase II Response Rate | Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin | At 3 months after initial treatment |
| Phase II Response Rate | Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin | At 6 months after initial treatment |
| Phase II Response Rate | Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin | At 9 months after initial treatment |
| Phase II Response Rate | Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin | At 1 year after initial treatment |
| Phase II Response Rate | Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin | Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days |
| Phase II Incidence of myeloid toxicity | Number of patients who develop myeloid toxicity while on study, defined as grade of anemia, neutropenia and thrombocytopenia CTCAE 4 | At 1 year |
| Phase II Incidence of secondary graft failure | Number of patients who develop secondary graft failure while on study, defined as: Either cytopenias after initial engraftment (ANC <500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was >5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced | At 1 year after initial treatment |
| Phase I incidence of VOD/SOS | Safety profile of intervention as measured by incidence of VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:
| At 1 year |
| Phase II rate of VOD/SOS - number of participants affected | Safety profile of intervention as measured by number of participants affected by VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:
| At 1 year |
| Phase II pharmacokinetic (PK) parameters - Cmax | Phase II PK parameter Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 1 Day 1 (C1D1) after 0 hours (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Cmax | Phase II PK parameter Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 1 Day 1 (C1D1) after 1 hour (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Cmax | Phase II PK parameter Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 1 Day 1 (C1D1) after 4 hours (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Cmax | Phase II PK parameter Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 1 Day 7 (C1D7) (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Cmax | Phase II PK parameter Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 2 Day 1 (C2D1) after 0 hours (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Cmax | Phase II PK parameter Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 2 Day 1 (C2D1) after 1 hour (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Cmax | Phase II PK parameter Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 4 Day 1 (C4D1) after 0 hours (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Cmax | Phase II PK parameter Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 4 Day 1 (C4D1) after 1 hour (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Ctrough | Phase II PK parameter Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 1 Day 1 (C1D1) after 0 hours (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Ctrough | Phase II PK parameter Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle1 Day 1 (C1D1) after 1 hour (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Ctrough | Phase II PK parameter Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle1 Day 1 (C1D1) after 4 hours (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Ctrough | Phase II PK parameter Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 1 Day 7 (C1D7) (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Ctrough | Phase II PK parameter Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 2 Day 1 (C2D1) after 0 hours (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Ctrough | Phase II PK parameter Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 2 Day 1 (C2D1) after 1 hour (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Ctrough | Phase II PK parameter Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 4 Day 1 (C4D1) after 0 hours (each cycle is 28 days) |
| Phase II pharmacokinetic (PK) parameters - Ctrough | Phase II PK parameter Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population. | At Cycle 4 Day 1 (C4D1) after 1 hour (each cycle is 28 days) |
| Dana-Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02215 | United States |
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| University of Nebraska Medical Center | Recruiting | Omaha | Nebraska | 68106 | United States |
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| Memorial Sloan Kettering Cancer Center | Active, not recruiting | New York | New York | 10065 | United States |
| University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center | Recruiting | Cleveland | Ohio | 44106-5065 | United States |
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| Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center | Active, not recruiting | Cleveland | Ohio | 44195 | United States |
| The James Cancer Hospital and Solove Research Institute | Recruiting | Columbus | Ohio | 43210 | United States |
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| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| 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 |