Leukemia, Lymphocytic, AcutePhase 2ZJU-HSCT-INONCT06861348
Effectiveness and Safety of InO±DLI for Relapsed B-ALL/LBL After Allo-HSCT
A Phase 2 study testing Inotuzumab Ozogamicin±Donor Lymphocyte Infusion in people with Leukemia, Lymphocytic, Acute, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
Trial summary
B cell acute lymphoblastic leukemia (B-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of B-lineage precursor cells. Read more about this study
- Who is it for?
- Ages 14 to 65 years
- Conditions the study is for
- Leukemia, Lymphocytic, Acute
- What is being tested?
- Inotuzumab Ozogamicin±Donor Lymphocyte Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2025to 30 Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Aged 14-65 years, male or female;
- Participants with CD22 positive B-ALL/LBL who relapsed after allo-HSCT from a related or unrelated donor (regardless of CD22 expression);
- ECOG physical status score 0~3, Karnofsky score ≥70;
- No active grade III/IV graft-versus-host disease (GvHD) or any active liver GvHD, no history of venous occlusive disease (VOD); No active GvHD and no previous history of VOD;
- Creatinine clearance rate≥50 mL/min (estimate by Cockcroft-Gault Equation);
- Liver function: alanine transaminase (ALT) and aspartate aminotransferase (AST)≤ 3×upper limit of normal (ULN), and total bilirubin ≤ 2×ULN;
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- Left ventricular ejection fraction (LVEF) ≥50% as measured by echocardiography;
- Estimated life expectancy >3 months;
- Participants voluntarily participate in clinical trial; Understand and know this study, sign an informed consent form, and be willing to follow all experimental procedures.
Who cannot join
- Allergic or with a history of serious adverse reactions to drugs or drugs with similar chemical structure in this study;
- Women who are pregnant or breastfeeding, as well as those who are unwilling to take effective contraceptive measures;
- Severe cardiac dysfunction: left ventricular ejection fraction (LVEF) <60%; Or severe arrhythmia: a history of a clinically significant corrected interval (QTc) prolongation (male >450ms; female>470 ms), ventricular tachycardia, atrial fibrillation, second degree atrioventricular block; myocardial infarction and coronary heart disease with clinical symptoms requiring medical treatment within one year before enrollment;
- Severe pulmonary disorders (obstructive or restrictive ventilation disorder);
- Severe liver function impairment: ALT, AST, or TBIL is more than 3 times higher than the upper limit of normal value (ULN);
- Severe renal impairment: serum Cr is more than 2 times higher than the upper limit of normal (ULN); Or 24-hour urinary creatinine clearance <50ml/min;
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- Participants with active infection or active bleeding who were deemed intolerance to InO treatment by the investigators;
- A history of new thrombosis, embolism, cerebral hemorrhage or other diseases within one year before enrollment;
- Participants suffer from known or other mental disorders that investigators are unable to obtain informed consent and may interfere with their ability to comply with research requirements;
- A history of major organ surgery within the past six weeks;
- Drug abuse or chronic alcohol abuse that may affect the study results;
- Participants with a history of organ transplantation other than HSCT (except BMT);
- Other situations identified by the investigator as unsuitable to participate in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou
Yi Luo, M.D., 86-13666609126, luoyijr@zju.edu.com
Honghu Li, M.D., +8618158514785, 21518022@zju.edu.cn
About this study
Official title: Effectiveness and Safety of Inotuzumab Ozogamicin±Donor Lymphocyte Infusion for Relapsed B Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma After Allogeneic Hematopoietic Stem Cell Transplantation：Phrase II, Multicenter Study
B cell acute lymphoblastic leukemia (B-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of B-lineage precursor cells. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curable therapy for ALL, especially for high-risk ALL patients. However, post-HSCT recurrence is the primary cause of transplant failure and salvage treatment option for this patient population are very limited. Current data showed that the CR rate and overall survival (OS) in adults with ALL who relapse after transplantation are as low as 30% and 25%, respectively, and the prognosis is extremely dismal. Some researchers have successfully salvage treated relapsed B-ALL patients after transplantation with donor lymphocyte infusions (DLI), but the response rate of DLI alone is usually less than 10%, with increased risk of Graft-Versus-Host Disease (GvHD). In the immunotherapy era, the introduction of immuno-designed therapies like bispecific antibody constructs, antibody conjugates, as well as chimeric antigen receptor T cell (CAR-T) therapy, have immensely broadened the treatment landscape of relapsed or refractory (r/r) B-ALL. Inotuzumab ozogamicin (InO) is a CD22-targeted monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. Based on the pivotal Phase III INO-VATE clinical trial published in N Engl J Med in 2016, compared to standard chemotherapy, 73% (64/88) of r/r B-ALL patients treated with InO achieved CR/CRi in the first cycle. Superior CR duration, OS and relapse free survival (RFS) was also observed in the InO group. Subgroup analysis showed that the treatment benefits were consistent for patients who relapsed after allo-HSCT. Moreover, a single-center retrospective study attempted to salvage treat relapsed B-ALL patients after transplantation with combined InO and DLI, results showed that six out of eight patients achieved CR after the first InO course and 75% of patients obtained MRD negativity after the second course, which is quite satisfactory. Therefore, we designed a Phase II clinical study of InO combined with or without DLI in patients with recurrent acute B-ALL/LBL after allo-HSCT, with expectation to increase CR rate and improve long-term survival.
- Conditions
- Leukemia, Lymphocytic, Acute
- Being tested
- Inotuzumab Ozogamicin±Donor Lymphocyte Infusion
- Keywords
- Inotuzumab Ozogamicin, Donor Lymphocyte Infusion, Relapsed B cell Acute Lymphoblastic Leukemia, Allogeneic Hematopoietic Stem Cell Transplantation
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inotuzumab Ozogamicin±Donor Lymphocyte InfusionDrug
Participants will receive Ino±DLI regimen:
- ① InO induction dose: the first cycle: 0.8mg/m2, intravenous infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15;
- ② If CR/CRi was reached after induction, the second cycle :0.5mg/m2, intravenous infusion, d1, d8，d15; If CR/CRi is not reached, Cycle 2 :0.8mg/m2, IV infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15;
- ③DLI dose: CD3 positive cells 1x10^7/kg; DLI indication: no previous grade III-IV aGVHD, negative HLALOSS test and no present aGVHD and cGVHD;
- Lumbar puncture: cytarabine 50mg+dexamethasone 5mg+methotrexate 10mg, intrathecal injection, once a month after remission, a total of 4-6 courses of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Ino±DLI regimen | Experimental | 1. InO induction：the first cycle: 0.8mg/m2, intravenous infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15. 2.InO consolidation：If CR/CRi was reached after induction, the second cycle :0.5mg/m2, intravenous infusion, d1, d8, d15; If CR/CRi is not reached, Cycle 2 :0.8mg/m2, IV infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15. 3. DLI: CD3 positive cells 1x10^7/kg; DLI indication: no previous grade III-IV aGVHD, negative HLALOSS test and no present aGVHD and cGVHD. Receives: Drug: Inotuzumab Ozogamicin±Donor Lymphocyte Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete remission rate (CRR)
CR was defined as bone marrow (BM) lymphoblasts≤5%, no evidence of active disease, and complete recovery of peripheral blood counts (platelet count >100×109/L, absolute neutrophil count >1×109/L); CRi was defined as BM lymphoblasts ≤5%, no evidence of active disease, and incomplete recovery of peripheral blood counts (platelet count>50×109/L and absolute neutrophil count >0.5×109/L). CR rate after InO treatment will be recorded.
Measured: 1 month after InO treatment
Secondary outcomes (6)
Duration of remission (DOR)
The period from the first evaluation of CR to the first evaluation of PD or death of any cause.
Measured: 2 year
Overall survival (OS)
The period from the first infusion to any cause of death.
Measured: 2 years
Progression-free survival (PFS)
The period from the day when the participant receives Ino treatment to the first recorded disease progression (whether treated or not) or death of any cause, which occurs first.
Measured: 2 years
Cumulative incidence of disease relapse or progression
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Measured: 2 year
Cumulative incidence of transplant-related nonrelapse mortality (NRM)
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Measured: 2 year
Incidence of Treatment Related adverse events (AEs)
Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs) assessed by NCI-CTCAE v5.0 criteria.
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2025
- Study start1 Mar 2025 (estimated)
- Primary completion30 Apr 2026 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Lymphocytic, AcuteStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Zhejiang UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yi Luo, First Affiliated Hospital of Zhejiang University
- Investigators
- Yi Luo, M.D., Principal investigator, First Affilaated Hospital of Medical School of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06861348
- Sponsor's protocol ID
- IIT20240086C-X1
- Acronym
- ZJU-HSCT-INO
- Status last verified
- Dec 2024
- First submitted
- 3 Mar 2025
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness and Safety of Inotuzumab Ozogamicin±Donor Lymphocyte Infusion for Relapsed B Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma After Allogeneic Hematopoietic Stem Cell Transplantation：Phrase II, Multicenter Study
- ClinicalTrials.gov ID
- NCT06861348
- Acronym / sponsor ID
- ZJU-HSCT-INO / IIT20240086C-X1
- Conditions
- Leukemia, Lymphocytic, Acute
- Keywords
- Inotuzumab Ozogamicin, Donor Lymphocyte Infusion, Relapsed B cell Acute Lymphoblastic Leukemia, Allogeneic Hematopoietic Stem Cell Transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 23 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Study start
- 1 Mar 2025 (estimated)
- Primary completion
- 30 Apr 2026 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 6 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
B cell acute lymphoblastic leukemia (B-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of B-lineage precursor cells. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curable therapy for ALL, especially for high-risk ALL patients. However, post-HSCT recurrence is the primary cause of transplant failure and salvage treatment option for this patient population are very limited. Current data showed that the CR rate and overall survival (OS) in adults with ALL who relapse after transplantation are as low as 30% and 25%, respectively, and the prognosis is extremely dismal. Some researchers have successfully salvage treated relapsed B-ALL patients after transplantation with donor lymphocyte infusions (DLI), but the response rate of DLI alone is usually less than 10%, with increased risk of Graft-Versus-Host Disease (GvHD). In the immunotherapy era, the introduction of immuno-designed therapies like bispecific antibody constructs, antibody conjugates, as well as chimeric antigen receptor T cell (CAR-T) therapy, have immensely broadened the treatment landscape of relapsed or refractory (r/r) B-ALL. Inotuzumab ozogamicin (InO) is a CD22-targeted monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. Based on the pivotal Phase III INO-VATE clinical trial published in N Engl J Med in 2016, compared to standard chemotherapy, 73% (64/88) of r/r B-ALL patients treated with InO achieved CR/CRi in the first cycle. Superior CR duration, OS and relapse free survival (RFS) was also observed in the InO group. Subgroup analysis showed that the treatment benefits were consistent for patients who relapsed after allo-HSCT. Moreover, a single-center retrospective study attempted to salvage treat relapsed B-ALL patients after transplantation with combined InO and DLI, results showed that six out of eight patients achieved CR after the first InO course and 75% of patients obtained MRD negativity after the second course, which is quite satisfactory. Therefore, we designed a Phase II clinical study of InO combined with or without DLI in patients with recurrent acute B-ALL/LBL after allo-HSCT, with expectation to increase CR rate and improve long-term survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ino±DLI regimen | Experimental | Drug: Inotuzumab Ozogamicin±Donor Lymphocyte Infusion1. InO induction：the first cycle: 0.8mg/m2, intravenous infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15. 2.InO consolidation：If CR/CRi was reached after induction, the second cycle :0.5mg/m2, intravenous infusion, d1, d8, d15; If CR/CRi is not reached, Cycle 2 :0.8mg/m2, IV infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15. 3. DLI: CD3 positive cells 1x10^7/kg; DLI indication: no previous grade III-IV aGVHD, negative HLALOSS test and no present aGVHD and cGVHD. |
Who may qualify
- Ages
- 14 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Aged 14-65 years, male or female;
- Participants with CD22 positive B-ALL/LBL who relapsed after allo-HSCT from a related or unrelated donor (regardless of CD22 expression);
- ECOG physical status score 0~3, Karnofsky score ≥70;
- No active grade III/IV graft-versus-host disease (GvHD) or any active liver GvHD, no history of venous occlusive disease (VOD); No active GvHD and no previous history of VOD;
- Creatinine clearance rate≥50 mL/min (estimate by Cockcroft-Gault Equation);
Key exclusion criteria (13 listed)
- Allergic or with a history of serious adverse reactions to drugs or drugs with similar chemical structure in this study;
- Women who are pregnant or breastfeeding, as well as those who are unwilling to take effective contraceptive measures;
- Severe cardiac dysfunction: left ventricular ejection fraction (LVEF) <60%; Or severe arrhythmia: a history of a clinically significant corrected interval (QTc) prolongation (male >450ms; female>470 ms), ventricular tachycardia, atrial fibrillation, second degree atrioventricular block; myocardial infarction and coronary heart disease with clinical symptoms requiring medical treatment within one year before enrollment;
- Severe pulmonary disorders (obstructive or restrictive ventilation disorder);
- Severe liver function impairment: ALT, AST, or TBIL is more than 3 times higher than the upper limit of normal value (ULN);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inotuzumab Ozogamicin±Donor Lymphocyte InfusionParticipants will receive Ino±DLI regimen: * ① InO induction dose: the first cycle: 0.8mg/m2, intravenous infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15; * ② If CR/CRi was reached after induction, the second cycle :0.5mg/m2, intravenous infusion, d1, d8，d15; If CR/CRi is not reached, Cycle 2 :0.8mg/m2, IV infusion, d1; 0.5 mg/m2, intravenous infusion, d8, d15; * ③DLI dose: CD3 positive cells 1x10^7/kg; DLI indication: no previous grade III-IV aGVHD, negative HLALOSS test and no present aGVHD and cGVHD; * Lumbar puncture: cytarabine 50mg+dexamethasone 5mg+methotrexate 10mg, intrathecal injection, once a month after remission, a total of 4-6 courses of treatment. | Drug | Ino±DLI regimen |
Primary outcome
complete remission rate (CRR)
Time frame: 1 month after InO treatment
CR was defined as bone marrow (BM) lymphoblasts≤5%, no evidence of active disease, and complete recovery of peripheral blood counts (platelet count >100×109/L, absolute neutrophil count >1×109/L); CRi was defined as BM lymphoblasts ≤5%, no evidence of active disease, and incomplete recovery of peripheral blood counts (platelet count>50×109/L and absolute neutrophil count >0.5×109/L). CR rate after InO treatment will be recorded.
6 secondary outcomes
Duration of remission (DOR)
Time frame: 2 year
Overall survival (OS)
Time frame: 2 years
Progression-free survival (PFS)
Time frame: 2 years
Cumulative incidence of disease relapse or progression
Time frame: 2 year
Cumulative incidence of transplant-related nonrelapse mortality (NRM)
Time frame: 2 year
Incidence of Treatment Related adverse events (AEs)
Time frame: 2 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yi Luo, M.D. principal investigator
First Affilaated Hospital of Medical School of Zhejiang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Inotuzumab Ozogamicin±Donor Lymphocyte Infusion in people with Leukemia, Lymphocytic, Acute, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yi Luo, M.D. (+8613666609126, luoyijr@zju.edu.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete remission rate (CRR) (time frame: 1 month after InO treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2025.