Precursor Cell Lymphoblastic LeukemiaPhase 2NCT03460522
Inotuzumab Ozogamicin and Conventional Chemotherapy In Patients Aged 56 Years and Older With ALL
A Phase 2 study testing Inotuzumab ozogamicin in people with Precursor Cell Lymphoblastic Leukemia, run by Nicola Goekbuget at 14 sites in Germany.
Trial summary
The trial proposed to evaluate the efficacy and safety of an inotuzumab ozogamicin followed by maintenance treatment in patients with acute lymphoblastic leukemia older than 56 years Read more about this study
- Who is it for?
- Ages 56 to 74 years
- Conditions the study is for
- Precursor Cell Lymphoblastic Leukemia
- What is being tested?
- Inotuzumab ozogamicin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 14 sitesGermany
- Study dates
- 2 May 2018to Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 56 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients, ≥56 years of age and contraindication for age-adapted consolidation chemotherapy due to age (≥75 years) and/or severe co-morbidities (>2 per Charlson Score).
- Newly diagnosed acute lymphoblastic leukemia (>25% marrow blasts, assessed by morphology; i.e. M3 marrow)
- Leukemic blasts must have CD22 surface expression of at least 20%, assessed by local/institutional flow cytometry of a bone marrow aspirate sample (assessment of CD22 via the reference lab for immunophenotyping is strongly recommended). In the case of an inadequate aspirate sample (dry tap), flow cytometry of peripheral blood specimen may be substituted if the patient has circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
- No previous ALL-specific treatment with the exception of corticosteroids and/or single dose vincristine and/or a maximum of three doses of cyclophosphamide (cumulative dose of 600 mg/m2) and the standard prephase treatment
- With or without documented CNS involvement
- Adequate liver function, including total serum bilirubin < 2.0 x upper limit of normal (ULN) unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) < 2.5 x ULN. If organ function abnormalities are considered due to leukemic infiltration of the liver, total serum bilirubin must be < 2.5 x ULN and AST/ALT < 5 x ULN
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- Serum creatinine <1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of >40 mL/min
- WHO performance status ≤ 2
- Signed written inform consent
- Inclusion in GMALL registry
Who cannot join
- Philadelphia-chromosome or BCR-ABL positive ALL
- Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria
- Peripheral absolute lymphoblast count >10,000/μL after pre-phase treatment and before start of study medication
- Known systemic vasculitis (e.g. , Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIV infection or severe inflammatory disease)
- Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV)
- Major surgery within < 4 weeks before entry on study
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- Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function or unstable pulmonary condition)
- Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery; patients with previous malignancies are eligible provided that they have been disease free for >2 years
- Cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than 45%, or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure
- Myocardial infarction < 6 months before entry on study
- History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block or higher degrees of AV block unless a permanent pacemaker has been implanted
- Uncontrolled electrolyte disorders that can confound the effects of a QTc prolonging drug (e.g., hypokalemia, hypocalcemia, hypomagnesemia)
- History of chronic liver disease (e.g., cirrhosis) or suspected alcohol abuse
- History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)
- Administration of live vaccine <6 weeks before entry on study
- Evidence of uncontrolled current serious active infection (including sepsis, bacteremia, fungemia or COVID-19 infection) or patients with a recent history (within 4 months) of deep tissue infections such as fasciitis or osteomyelitis
- Patients who have had a severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibodies or any known hypersensitivity to the active substance or any of its excipients
- Pregnant females; breastfeeding females; males and females of childbearing potential (a woman is considered of childbearing potential (WOCBP) i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile e.g. after hysterectomy or bilateral ovariectomy. Please refer to chapter 12.4 Contraceptive Requirements.) not using highly effective contraception or not agreeing to continue highly effective contraception for women at least 8 months and for men at least 5 months after the last dose of investigational product
- 18. Participation in other studies involving investigational drug(s) (Phase I-IV) within 4 weeks before study inclusion
- 19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Germany14 sites, 14 recruiting
- Recruiting
Klinikum Augsburg
Augsburg
Andreas Rank, PD Dr
- Recruiting
Universität Bonn
Bonn
Katjana Schwab, Dr
- Recruiting
Klinikum Chemnitz gGmbH
Chemnitz
Mathias Hänel, PD Dr
- Recruiting
Uniklinik Dresden
Dresden
Nael Alakel, Dr.
- Recruiting
University Hospital Düsseldorf
Düsseldorf, 40225
Kathrin Nachtkamp, Dr
- Recruiting
Universität Erlangen
Erlangen
Bernd Spriewald, Prof
- Recruiting
Univeristätsklinikum Essen
Essen
Maher Hanoun, PD Dr.
- Recruiting
University Hospital of Frankfurt
Frankfurt, 60590
Nicola Gökbuget, Dr
- Recruiting
Universitätsklinikum Freiburg
Freiburg im Breisgau
Ralph Wäsch, Prof. Dr.
- Recruiting
Universitätsklinikum Heidelberg
Heidelberg, 69120
Simon Raffel, Dr
- Recruiting
Uniklinikum
Jena
Sebastian Scholl, PD Dr
- Recruiting
University of Muenster
Münster, 48149
Matthias Stelljes, Prof Dr
- Recruiting
Klinikum Nürnberg Nord
Nuremberg
Kerstin Schäfer-Eckhardt, Dr
- Recruiting
Robert - Bosch - Krankenhaus
Stuttgart
Sonja Martin, Dr.
About this study
Official title: Open Label Phase II Study to Evaluate the Efficacy and Safety of Inotuzumab Ozogamicin for Induction Followed by Chemotherapy Consolidation and Maintenance Therapy In Patients Aged 56 Years and Older With Acute Lymphoblastic Leukemia (ALL)
The trial proposed to evaluate the efficacy and safety of an inotuzumab ozogamicin followed by maintenance treatment in patients with acute lymphoblastic leukemia older than 56 years
Read the detailed description
Despite recent advances especially in younger patients, the prognosis of elderly patients with ALL remains dismal with a 5-year survival rate of around 20%, even after intensive chemotherapy.
Inotuzumab ozogamicin (PF-05208773; CMC-544) is an antibody-targeted intravenous (IV) chemotherapy agent composed of an anti-CD22 antibody linked to calicheamicin, a potent cytotoxic antitumor antibiotic.
After a prephase treatment, induction therapy will be based on three cycles of inotuzumab ozogamicin and intrathecal therapy only. This will be followed by a conventional maintenance therapy. All patients will be followed for cytological response, minimal residual disease and safety parameters.
- Conditions
- Precursor Cell Lymphoblastic Leukemia
- Being tested
- Inotuzumab ozogamicin
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inotuzumab ozogamicinDrug
Patients will receive standard of care chemotherapy (only maintenance) after Inotuzumab Ozogamicin.
| Study group | Role | What they receive |
|---|---|---|
| Induction Therapy with Inotuzumab Ozogamicin | Experimental | Patients will receive up to 3 cycles Inotuzumab with applications on day 1, 8 and 15 in each cycle. First dose will be 0.8 mg/m² on Day 1. All subsequent doses will be 0,5 mg/m². Receives: Drug: Inotuzumab ozogamicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event free survival (EFS) at 12-months follow-up
An event is any of the following: persisting bone marrow blasts (more than 5% leukemic blasts) after two cycles of inotuzumab ozogamicin, relapse or death.
Measured: At 12 months
Secondary outcomes (7)
Complete hematological remission
The rate of complete hematological remission after inotuzumab ozogamicin induction treatment
Measured: 42 days
MRD response after induction treatment
The rate of patients being negative for minimal residual disease (defined by RQ-PCR for at least one leukemia-specific IG/TR gene rearrangement or leukemia specific genetic aberration with a sensitivity of at least 10-4) after induction treatment
Measured: 42 days
Relapse free survival
Relapse free survival after two years
Measured: two years
Molecular relapse
The proportion of patients with molecular relapse
Measured: two years
Overall survival
Overall survival after two years
Measured: two years
Death during induction
Death during induction
Measured: 42 days
Death in complete remission
Death in complete remission
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2018
- Study start2 May 2018
- Primary completionJun 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Precursor Cell Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- 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
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nicola Goekbuget
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nicola Goekbuget, Goethe University
- Investigators
- Matthias Stelljes, MD, Principal investigator, Universität Münster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03460522
- Sponsor's protocol ID
- INITIAL-1
- Status last verified
- Oct 2022
- First submitted
- 22 Feb 2018
- Last updated
- 2 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 41671463Stelljes M, Raffel S, Alakel N, Wasch R, Kondakci M, Scholl S, Rank A, Hanel M, Spriewald B, Hanoun M, Martin S, Schwab K, Serve H, Reiser L, Knaden J, Pfeifer H, Marx J, Sauer T, Berdel WE, Lenz G, Bruggemann M, Gokbuget N, Wethmar K. Inotuzumab Ozogamicin as Induction Therapy for Patients Older Than 55 Years With Philadelphia Chromosome-Negative B-Precursor ALL. J Clin Oncol. 2024 Jan 20;42(3):273-282. doi: 10.1200/JCO.23.00546. Epub 2023 Oct 26.
PubMed 37883727
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Phase II Study to Evaluate the Efficacy and Safety of Inotuzumab Ozogamicin for Induction Followed by Chemotherapy Consolidation and Maintenance Therapy In Patients Aged 56 Years and Older With Acute Lymphoblastic Leukemia (ALL)
- ClinicalTrials.gov ID
- NCT03460522
- Acronym / sponsor ID
- INITIAL-1
- Conditions
- Precursor Cell Lymphoblastic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Nicola GoekbugetUniversity, hospital or other
- Study start
- 2 May 2018 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 9 Mar 2018 (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.
The trial proposed to evaluate the efficacy and safety of an inotuzumab ozogamicin followed by maintenance treatment in patients with acute lymphoblastic leukemia older than 56 years
Detailed description
Despite recent advances especially in younger patients, the prognosis of elderly patients with ALL remains dismal with a 5-year survival rate of around 20%, even after intensive chemotherapy.
Inotuzumab ozogamicin (PF-05208773; CMC-544) is an antibody-targeted intravenous (IV) chemotherapy agent composed of an anti-CD22 antibody linked to calicheamicin, a potent cytotoxic antitumor antibiotic.
After a prephase treatment, induction therapy will be based on three cycles of inotuzumab ozogamicin and intrathecal therapy only. This will be followed by a conventional maintenance therapy. All patients will be followed for cytological response, minimal residual disease and safety parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Induction Therapy with Inotuzumab Ozogamicin | Experimental | Drug: Inotuzumab ozogamicinPatients will receive up to 3 cycles Inotuzumab with applications on day 1, 8 and 15 in each cycle. First dose will be 0.8 mg/m² on Day 1. All subsequent doses will be 0,5 mg/m². |
Who may qualify
- Ages
- 56 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patients, ≥56 years of age and contraindication for age-adapted consolidation chemotherapy due to age (≥75 years) and/or severe co-morbidities (>2 per Charlson Score).
- Newly diagnosed acute lymphoblastic leukemia (>25% marrow blasts, assessed by morphology; i.e. M3 marrow)
- Leukemic blasts must have CD22 surface expression of at least 20%, assessed by local/institutional flow cytometry of a bone marrow aspirate sample (assessment of CD22 via the reference lab for immunophenotyping is strongly recommended). In the case of an inadequate aspirate sample (dry tap), flow cytometry of peripheral blood specimen may be substituted if the patient has circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
- No previous ALL-specific treatment with the exception of corticosteroids and/or single dose vincristine and/or a maximum of three doses of cyclophosphamide (cumulative dose of 600 mg/m2) and the standard prephase treatment
- With or without documented CNS involvement
Key exclusion criteria (20 listed)
- Philadelphia-chromosome or BCR-ABL positive ALL
- Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria
- Peripheral absolute lymphoblast count >10,000/μL after pre-phase treatment and before start of study medication
- Known systemic vasculitis (e.g. , Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIV infection or severe inflammatory disease)
- Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV)
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 ozogamicinPatients will receive standard of care chemotherapy (only maintenance) after Inotuzumab Ozogamicin. | Drug | Induction Therapy with Inotuzumab Ozogamicin |
Primary outcome
Event free survival (EFS) at 12-months follow-up
Time frame: At 12 months
An event is any of the following: persisting bone marrow blasts (more than 5% leukemic blasts) after two cycles of inotuzumab ozogamicin, relapse or death.
7 secondary outcomes
Complete hematological remission
Time frame: 42 days
MRD response after induction treatment
Time frame: 42 days
Relapse free survival
Time frame: two years
Molecular relapse
Time frame: two years
Overall survival
Time frame: two years
Death during induction
Time frame: 42 days
Death in complete remission
Time frame: up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2022.
- Derived from this study: PubMed 41671463Davis 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.
- Derived from this study: PubMed 37883727Stelljes M, Raffel S, Alakel N, Wasch R, Kondakci M, Scholl S, Rank A, Hanel M, Spriewald B, Hanoun M, Martin S, Schwab K, Serve H, Reiser L, Knaden J, Pfeifer H, Marx J, Sauer T, Berdel WE, Lenz G, Bruggemann M, Gokbuget N, Wethmar K. Inotuzumab Ozogamicin as Induction Therapy for Patients Older Than 55 Years With Philadelphia Chromosome-Negative B-Precursor ALL. J Clin Oncol. 2024 Jan 20;42(3):273-282. doi: 10.1200/JCO.23.00546. Epub 2023 Oct 26.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Matthias Stelljes, MD principal investigator
Universität Münster
14 sites 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 in people with Precursor Cell Lymphoblastic Leukemia, run by Nicola Goekbuget at 14 sites in Germany.
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 10 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 2 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Germany. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Matthias Stelljes (Principal Investigator), MD (+49 (0)251 8352801, stelljes@uni-muenster.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event free survival (EFS) at 12-months follow-up (time frame: At 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03460522, which also lists 2 linked publications.
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 2 Nov 2022.