NCT03104491 · Leland Metheny
Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Inotuzumab Ozogamicin
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)
Primary outcome measures
Phase I MTD
Time frame: Up to 112 days (16 weeks)
Defined post hematopoietic stem cell transplantation MTD
Phase I DLTs
Time frame: Up to 112 days (16 weeks)
Frequency of DLTs during the first two cycles in ALL-participants
Phase II Median DFS
Time frame: At 3 months after initial treatment
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
Phase II Median DFS
Time frame: At 6 months after initial treatment
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
Phase II Median DFS
Time frame: At 9 months after initial treatment
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
Phase II Median DFS
Time frame: At 1 year after initial treatment
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
Phase II Median DFS
Time frame: Post first dose of inotuzumab ozogamicin
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
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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:
- Creatinine clearance \< 30ml/min
- Bilirubin \> 2X institutional upper limit of normal
- AST (SGOT) \> 2X institutional upper limit of normal
- ALT (SGPT) \> 2X institutional upper limit of normal
- 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
Where
- Westwood, Kansas
- Boston, Massachusetts
- Omaha, Nebraska
- New York, New York
- Cleveland, Ohio
- Columbus, Ohio
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 10, 2026 · Source of record for eligibility and locations