Philadelphia-Negative ALLPhase 2NCT04334993
Pediatric-type Therapy With Pre-transplant Blinatumomab for HR Patients - Phase II Study
A Phase 2 study testing Blinatumomab in people with Philadelphia-Negative ALL and High-Risk Cancer, run by Israeli Medical Association at 4 sites in Israel.
Trial summary
Despite recent therapeutic advancements, the outcome of young adults with Philadelphia-negative (Ph-neg) acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) remains unsatisfactory, especially in those patients with high-risk disease features. Read more about this study
- Who is it for?
- Ages 18 to 30 years
- Conditions the study is for
- Philadelphia-Negative ALL, High-Risk Cancer
- What is being tested?
- Blinatumomab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 4 sitesIsrael
- Study dates
- 1 Jan 2021to 1 May 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 18 to 30 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age ≥ 18 years and <30 years of age at the time of signing the informed consent document.
- Have a documented diagnosis of Ph-neg ALL, LBL or MPAL according to the WHO 2016 classification (appendix I).
- Females of childbearing potential (FCBP) may participate, providing they meet the following conditions:
- Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study, and for 3 months following EOT; and have a negative serum or urine pregnancy test (investigator's discretion; sensitivity at least 25 mIU/mL) at screening; and have a negative serum or urine pregnancy test (investigator's discretion) within 72 hours prior to starting study therapy in the treatment phase (note that the screening serum pregnancy test can be used as the test prior to starting study therapy in treatment phase if it is performed within the 72-hour timeframe).
- Male subjects with a female partner of childbearing potential must agree to the use of at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for 3 months following the last dose of study drug.
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
- Able to adhere to the study visit schedule and other protocol requirements.
Who cannot join
- Age <18 or over 30 years at the time of signing the informed consent document.
- Ph-positive disease.
- Known Human Immunodeficiency Virus (HIV).
- Known or suspected hypersensitivity to any of the study drugs.
- Pregnant or lactating females.
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Participation to an investigational drug trial in the last month before randomization.
Trial locations and contacts
4 sites in 1 country.
Israel4 sites, 4 recruiting
- Recruiting
Rambam Medical Center
Haifa
Yishai Ofran, MD, y_ofran@rambam.health.gov.il
- Recruiting
Shaarei Tzedek Medical Center
Jerusalem
Jacob Rowe, MD, rowe@rambam.health.gov.il
- Recruiting
Rabin Medical Center
Petah Tikva, 49100
Ofir Wolach, MD, +972-3-937-8116, ofirw@clalit.org.il
Miri Pinhasov, MA, +972-3-9378078, miripi@clalit.org.il
- Not yet recruiting
Tel Aviv Medical Center
Tel Aviv
Yakir Moshe, MD PhD, yakirm@tlvmc.gov.il
About this study
Official title: A Phase 2, Multicenter, Single Arm Trial to Assess the Safety and Efficacy of a Pediatric Approach to for Young Adults With Acute Lymphoblastic Leukemia With Blinatumomab Therapy for High-risk Patients Prior to Allogeneic Transplantation
Despite recent therapeutic advancements, the outcome of young adults with Philadelphia-negative (Ph-neg) acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) remains unsatisfactory, especially in those patients with high-risk disease features. In young adults pediatric-based chemotherapy approaches improve outcome. Furthermore, there is evidence that pre-transplant antibody-based therapy may render patients with positive minimal residual disease (MRD+) to an MRD-negative status (MRD-) and that this may be associated with improved post-transplant outcome.
This is prospective study to evaluate the potential benefit of a modified pediatric-based approach in young adults with Ph-neg ALL. Safety and efficacy of pre-transplant antibody-based consolidation in high-risk patients with Ph-neg ALL will be performed.
Read the detailed description
This is a national, multicenter, phase II clinical trial to evaluate the potential benefit of a modified pediatric-based approach in young adults with Ph-neg ALL. Safety and efficacy of pre-transplant antibody-based consolidation in high-risk patients with Ph-neg ALL will be assessed.
Young-adult patients eligible with Ph-neg ALL, LBL and mixed phenotype acute leukemia (MPAL) will undergo risk stratification and started on the pediatric Italian Association of Pediatric Hematology Oncology-Berlin-Frankfurt-Münster (AIEOP-BFM) 2009 protocol. Patients defined as having non-high-risk disease features (non-HR) as defined by MRD and/or cytogenetic criteria will complete the non-HR chemotherapy arm per protocol. Patients designated as having HR disease features after 2 induction blocks will be treated with CNS directed block followed by up to 2 cycles of blinatumomab (for B-cell ALL) followed by allogeneic stem cell transplantation. All patients will be centrally assessed for MRD and for Ph-like status.
- Conditions
- Philadelphia-Negative ALL, High-Risk Cancer
- Being tested
- Blinatumomab
- Keywords
- Philadelphia-Negative ALL, Pediatric therapy, Blinatumomab, Allogeneic transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BlinatumomabDrug
Also called AIEOP-BFM 2009 protocol - multiagent chemothertapy protocol backbone
Patients with high risk disease features after 2 induction blocks as defined per protocol will be treated with CNS directed block followed by up to 2 cycles of blinatumomab (for B-cell ALL) followed by allogeneic stem cell transplantation.
| Study group | Role | What they receive |
|---|---|---|
| Blinatumomab pre-transplant to high risk Ph-negative ALL pts. | Experimental | Patients designated high risk based on protocol will receive 2 cycles of therapy followed by allogeneic transplantation. Patients ≥45 kg (fixed dose): Cycles 1 and 2: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle. Receives: Drug: Blinatumomab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
Measured from the date of entry on study until treatment failure, relapse from CR, or death from any cause, whichever occurs first
Measured: 2 years
Secondary outcomes (3)
Overall survival (OS)
Measured from the date of entry on study until until death from any cause
Measured: 2 years
Early death during induction
Death during the first 60 days from entering study from any cause
Measured: 60 days
MRD status
MRD status pre- and post-antibody-based therapy
Measured: MRD will be assess by PCR after induction I (day 33), after induction II (week 12), after blinatumomab therapy (prior to HSCT) and at days 30 and 100 post alloHSCT.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start1 Jan 2021
- Primary completion1 May 2023 (estimated)
- Study completion1 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Philadelphia-Negative ALLStudies 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
- Model description
- This is a national, multicenter, phase II clinical trial
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Israeli Medical Association
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04334993
- Sponsor's protocol ID
- AYA001
- Status last verified
- Aug 2020
- First submitted
- 31 Mar 2020
- Last updated
- 7 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: All data will be coded and uploaded to an electronic CRF (red-cap) to manage abnd analyze data
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 41671463
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Single Arm Trial to Assess the Safety and Efficacy of a Pediatric Approach to for Young Adults With Acute Lymphoblastic Leukemia With Blinatumomab Therapy for High-risk Patients Prior to Allogeneic Transplantation
- ClinicalTrials.gov ID
- NCT04334993
- Acronym / sponsor ID
- AYA001
- Conditions
- Philadelphia-Negative ALL, High-Risk Cancer
- Keywords
- Philadelphia-Negative ALL, Pediatric therapy, Blinatumomab, Allogeneic transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Israeli Medical AssociationUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 1 May 2023 (estimated)
- Study completion
- 1 May 2025 (estimated)
- First posted
- 6 Apr 2020 (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.
Despite recent therapeutic advancements, the outcome of young adults with Philadelphia-negative (Ph-neg) acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) remains unsatisfactory, especially in those patients with high-risk disease features. In young adults pediatric-based chemotherapy approaches improve outcome. Furthermore, there is evidence that pre-transplant antibody-based therapy may render patients with positive minimal residual disease (MRD+) to an MRD-negative status (MRD-) and that this may be associated with improved post-transplant outcome.
This is prospective study to evaluate the potential benefit of a modified pediatric-based approach in young adults with Ph-neg ALL. Safety and efficacy of pre-transplant antibody-based consolidation in high-risk patients with Ph-neg ALL will be performed.
Detailed description
This is a national, multicenter, phase II clinical trial to evaluate the potential benefit of a modified pediatric-based approach in young adults with Ph-neg ALL. Safety and efficacy of pre-transplant antibody-based consolidation in high-risk patients with Ph-neg ALL will be assessed.
Young-adult patients eligible with Ph-neg ALL, LBL and mixed phenotype acute leukemia (MPAL) will undergo risk stratification and started on the pediatric Italian Association of Pediatric Hematology Oncology-Berlin-Frankfurt-Münster (AIEOP-BFM) 2009 protocol. Patients defined as having non-high-risk disease features (non-HR) as defined by MRD and/or cytogenetic criteria will complete the non-HR chemotherapy arm per protocol. Patients designated as having HR disease features after 2 induction blocks will be treated with CNS directed block followed by up to 2 cycles of blinatumomab (for B-cell ALL) followed by allogeneic stem cell transplantation. All patients will be centrally assessed for MRD and for Ph-like status.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a national, multicenter, phase II clinical trial
| Arm | Type | Receives |
|---|---|---|
| Blinatumomab pre-transplant to high risk Ph-negative ALL pts. | Experimental | Drug: BlinatumomabPatients designated high risk based on protocol will receive 2 cycles of therapy followed by allogeneic transplantation. Patients ≥45 kg (fixed dose): Cycles 1 and 2: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years and <30 years of age at the time of signing the informed consent document.
- Have a documented diagnosis of Ph-neg ALL, LBL or MPAL according to the WHO 2016 classification (appendix I).
- Females of childbearing potential (FCBP) may participate, providing they meet the following conditions:
- Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study, and for 3 months following EOT; and have a negative serum or urine pregnancy test (investigator's discretion; sensitivity at least 25 mIU/mL) at screening; and have a negative serum or urine pregnancy test (investigator's discretion) within 72 hours prior to starting study therapy in the treatment phase (note that the screening serum pregnancy test can be used as the test prior to starting study therapy in treatment phase if it is performed within the 72-hour timeframe).
- Male subjects with a female partner of childbearing potential must agree to the use of at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for 3 months following the last dose of study drug.
Key exclusion criteria (8 listed)
- Age <18 or over 30 years at the time of signing the informed consent document.
- Ph-positive disease.
- Known Human Immunodeficiency Virus (HIV).
- Known or suspected hypersensitivity to any of the study drugs.
- Pregnant or lactating females.
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 |
|---|---|---|
| BlinatumomabAlso: AIEOP-BFM 2009 protocol - multiagent chemothertapy protocol backbonePatients with high risk disease features after 2 induction blocks as defined per protocol will be treated with CNS directed block followed by up to 2 cycles of blinatumomab (for B-cell ALL) followed by allogeneic stem cell transplantation. | Drug | Blinatumomab pre-transplant to high risk Ph-negative ALL pts. |
Primary outcome
Event-free survival (EFS)
Time frame: 2 years
Measured from the date of entry on study until treatment failure, relapse from CR, or death from any cause, whichever occurs first
3 secondary outcomes
Overall survival (OS)
Time frame: 2 years
Early death during induction
Time frame: 60 days
MRD status
Time frame: MRD will be assess by PCR after induction I (day 33), after induction II (week 12), after blinatumomab therapy (prior to HSCT) and at days 30 and 100 post alloHSCT.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2021.
- 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.
- Individual participant dataSharing planned: No. All data will be coded and uploaded to an electronic CRF (red-cap) to manage abnd analyze data
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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.
4 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 Blinatumomab in people with Philadelphia-Negative ALL and High-Risk Cancer, run by Israeli Medical Association at 4 sites in Israel.
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 7 inclusion and 8 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 7 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Israel. 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 Ofir Wolach, MD (+972-3-9378116, ofirw@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (EFS) (time frame: 2 years). 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 NCT04334993, which also lists 1 linked publication.
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 7 May 2021.