Adult B Acute Lymphoblastic LeukemiaPhase 2NCT02997761
Ibrutinib and Blinatumomab in Treating Patients With Relapsed or Refractory B Acute Lymphoblastic Leukemia
A Phase 2 study testing Blinatumomab and Ibrutinib in people with Adult B Acute Lymphoblastic Leukemia and Philadelphia Chromosome Positive, run by University of California, Davis at 2 sites in United States.
Trial summary
This phase II trial studies how well ibrutinib and blinatumomab work in treating patients with B acute lymphoblastic leukemia that has come back or is not responding to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Positive
- What is being tested?
- Blinatumomab and Ibrutinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Jun 2017to 17 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed diagnosis of relapsed or refractory B-cell acute lymphoblastic leukemia/lymphoma with measurable bone marrow lymphoblasts or biopsy-proven extramedullary site measurable by computed tomography (CT) or positron emission tomography (PET)/CT imaging; Philadelphia chromosome-positive (Ph+) B-ALL patients must have failed treatment with at least one second generation tyrosine kinase inhibitor; prior allo-HCT is allowed
- No hematologic parameters for inclusion; transfusion-dependent patients are eligible and platelet counts should be maintained greater than 10,000/mm^3 throughout cycles 1 and 2
- Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (unless bilirubin rise is due to Gilbert's syndrome or B-ALL or non-hepatic origin)
- Serum aspartate transaminase (aspartate aminotransferase [AST]) or alanine transaminase (alanine aminotransferase [ALT]) less than or equal to 3 x ULN (unless due to B-ALL)
- Estimated creatinine clearance greater than or equal to 30 ml/min (Cockcroft-Gault) or serum creatinine less than or equal to 2 x ULN
- Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) =< 1.5 x ULN (unless B-ALL related)
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- Karnofsky performance status (KPS) performance status of 60% or greater
- Ability to understand and willingness to sign an informed consent form
- Ability to adhere to the study visit schedule and other protocol requirements
- Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for >= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy); female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study drug administration
- Male and female subjects who agree to use both a highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier method (e.g. condoms, vaginal ring, sponge, etc) during the period of therapy and for 90 days after the last dose of study drug
- Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of ibrutinib or blinatumomab will be determined following review of their case by the investigator
Who cannot join
- Diagnosis of T acute lymphoblastic leukemia (T-ALL) or Burkitt's leukemia/lymphoma
- Patients with current evidence of active central nervous system (CNS) leukemia
- History of treatment with ibrutinib or blinatumomab
- Investigational therapy, chemotherapy, immunotherapy, radiotherapy, or systemic graft versus host disease (GVHD) therapy within two weeks or five half-lives (whichever is shorter); steroids, hydroxyurea and/or leukapheresis are allowed to control blast count prior to the first dose of study drug
- Prior allo-HCT less than three months from the time of enrollment
- Any active acute GVHD or chronic GVHD greater than grade 1
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib and blinatumomab or other agents used in this study
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- Recent culture-documented infection requiring intravenous antimicrobials that was completed =< 7 days before the first dose of study drug or any uncontrolled active systemic infection; fever of unknown origin is not an exclusion criterion, as this may be disease-related
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version [v]4.03), grade =< 2, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded; subjects with HIV must have a CD4 count at or above the institutional lower limit of normal and not taking prohibited CYP3A strong inhibitors
- Major surgery within 4 weeks of first dose of study drug
- Any life-threatening illness, medical condition, or organ system dysfunction, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active autoimmune disorder, or psychiatric illness/social situations that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk; currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
- History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, adequately treated in situ carcinoma of the breast or cervix uteri, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; malignancy treated with curative intent with no known active disease present for >= 3 years
- Concomitant use of warfarin or other Vitamin K antagonists
- Subjects who received a strong cytochrome P 450 3A (CYP3A) inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP3A inhibitor
- Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification
- Breastfeeding or pregnant
- Participation in clinical trials with other investigational agents not included in this trial throughout the duration of this trial
- Unwilling or unable to participate in all required study evaluations and procedures or unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: A Phase 2 Study of Ibrutinib and Blinatumomab in Relapsed and Refractory B-Cell Acute Lymphoblastic Leukemia
This phase II trial studies how well ibrutinib and blinatumomab work in treating patients with B acute lymphoblastic leukemia that has come back or is not responding to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer cells to grow and spread. Giving ibrutinib and blinatumomab may work better in treating patients with relapsed or refractory B acute lymphoblastic leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of ibrutinib and blinatumomab in patients with relapsed or refractory B acute lymphoblastic leukemia (B-ALL) as measured by complete response (CR) rate.
SECONDARY OBJECTIVES:
- To further examine the efficacy and safety of ibrutinib and blinatumomab in patients with relapsed or refractory B-ALL as measured by overall response rate (ORR, defined as CR plus CR with incomplete count recovery [CRi]), relapse free survival (RFS), overall survival (OS), minimal residual disease (MRD) response, proportion of patients bridged to allogeneic hematopoietic cell transplant (allo-HCT), and toxicity.
- Being tested
- Blinatumomab, Ibrutinib
- Medical subject headings
- Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BlinatumomabBiological
Also called Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538
Given IV
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ibrutinib, blinatumomab) | Experimental | INDUCTION THERAPY: Patients receive ibrutinib PO QD on days 1-49 of course 1 and days 1-42 of course 2, and blinatumomab IV on days 8-35 of course 1 and days 1-28 of course 2 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients with CR/CRi after Induction Therapy receive ibrutinib PO QD on days 1-42 and blinatumomab IV on days 1-28. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Blinatumomab; Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Complete Remission (CR).
Defined as the number of participants who achieve CR according to National Comprehensive Cancer Network (NCCN) Guidelines for Acute Lymphoblastic Leukemia (ALL), Version 2.2015
Measured: Up to about 3 months from start of study treatment.
Secondary outcomes (5)
Number of Participants With Adverse Events
Number of participants with adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Measured: Up to about 8 months from start of study treatment.
Minimal Residual Disease (MRD) Negative CR/CRi Rate
Multiparameter Flow Cytometry (MFC) minimal residual disease (MRD) negative CR/CRi rate - defined as the number of CR/CRi participants with B-ALL cells comprising < 0.01% of bone marrow mononuclear cells [BMMC] as measured by flow cytometry or molecular studies.
Measured: Up to about 8 months from start of treatment.
Overall Response Rate (ORR).
Overall response rate (ORR) - defined as CR plus CR with incomplete count recovery (CRi) according to NCCN guidelines for ALL.
Measured: Up to 8 months from start of treatment.
Overall Survival (OS).
Defined as the median OS measured from the time of first study drug administration until the date of progression or death from any cause.
Measured: From the time of first study drug administration until date of death from any cause, assessed for up to about 15.6 months.
Proportion of Patients Bridged to Allogeneic Hematopoietic Cell Transplant (Allo-HCT or CAR-T.
Proportion of patients bridged to allogeneic hematopoietic cell transplant (allo-HCT or CAR-T.
Measured: Time from start of treatment to date of hematopoietic cell transplant assessed for up to 8 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study start27 Jun 2017
- Primary completion17 Jul 2025
- Study completion17 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult B Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Pharmacyclics LLC.
- Responsible party
- Principal investigator, Brian Jonas, University of California, Davis
- Investigators
- Brian Jonas, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02997761
- Sponsor's protocol ID
- 945122
- Other IDs
- UCDCC#266, UCDCC#266, P30CA093373, NCI-2016-01882
- Status last verified
- Jun 2026
- First submitted
- 12 Dec 2016
- Last updated
- 9 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Ibrutinib and Blinatumomab in Relapsed and Refractory B-Cell Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT02997761
- Acronym / sponsor ID
- 945122
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Pharmacyclics LLC.
- Study start
- 27 Jun 2017 (actual)
- Primary completion
- 17 Jul 2025 (actual)
- Study completion
- 17 Jul 2025 (actual)
- First posted
- 20 Dec 2016 (estimated)
- Results
- Posted 9 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well ibrutinib and blinatumomab work in treating patients with B acute lymphoblastic leukemia that has come back or is not responding to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer cells to grow and spread. Giving ibrutinib and blinatumomab may work better in treating patients with relapsed or refractory B acute lymphoblastic leukemia.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of ibrutinib and blinatumomab in patients with relapsed or refractory B acute lymphoblastic leukemia (B-ALL) as measured by complete response (CR) rate.
SECONDARY OBJECTIVES:
- To further examine the efficacy and safety of ibrutinib and blinatumomab in patients with relapsed or refractory B-ALL as measured by overall response rate (ORR, defined as CR plus CR with incomplete count recovery [CRi]), relapse free survival (RFS), overall survival (OS), minimal residual disease (MRD) response, proportion of patients bridged to allogeneic hematopoietic cell transplant (allo-HCT), and toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ibrutinib, blinatumomab) | Experimental | Biological: Blinatumomab, Drug: IbrutinibINDUCTION THERAPY: Patients receive ibrutinib PO QD on days 1-49 of course 1 and days 1-42 of course 2, and blinatumomab IV on days 8-35 of course 1 and days 1-28 of course 2 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients with CR/CRi after Induction Therapy receive ibrutinib PO QD on days 1-42 and blinatumomab IV on days 1-28. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Pathologically confirmed diagnosis of relapsed or refractory B-cell acute lymphoblastic leukemia/lymphoma with measurable bone marrow lymphoblasts or biopsy-proven extramedullary site measurable by computed tomography (CT) or positron emission tomography (PET)/CT imaging; Philadelphia chromosome-positive (Ph+) B-ALL patients must have failed treatment with at least one second generation tyrosine kinase inhibitor; prior allo-HCT is allowed
- No hematologic parameters for inclusion; transfusion-dependent patients are eligible and platelet counts should be maintained greater than 10,000/mm^3 throughout cycles 1 and 2
- Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (unless bilirubin rise is due to Gilbert's syndrome or B-ALL or non-hepatic origin)
- Serum aspartate transaminase (aspartate aminotransferase [AST]) or alanine transaminase (alanine aminotransferase [ALT]) less than or equal to 3 x ULN (unless due to B-ALL)
- Estimated creatinine clearance greater than or equal to 30 ml/min (Cockcroft-Gault) or serum creatinine less than or equal to 2 x ULN
Key exclusion criteria (22 listed)
- Diagnosis of T acute lymphoblastic leukemia (T-ALL) or Burkitt's leukemia/lymphoma
- Patients with current evidence of active central nervous system (CNS) leukemia
- History of treatment with ibrutinib or blinatumomab
- Investigational therapy, chemotherapy, immunotherapy, radiotherapy, or systemic graft versus host disease (GVHD) therapy within two weeks or five half-lives (whichever is shorter); steroids, hydroxyurea and/or leukapheresis are allowed to control blast count prior to the first dose of study drug
- Prior allo-HCT less than three months from the time of enrollment
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: Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538Given IV | Biological | Treatment (ibrutinib, blinatumomab) |
| IbrutinibAlso: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Given PO | Drug | Treatment (ibrutinib, blinatumomab) |
Primary outcome
Rate of Complete Remission (CR).
Time frame: Up to about 3 months from start of study treatment.
Defined as the number of participants who achieve CR according to National Comprehensive Cancer Network (NCCN) Guidelines for Acute Lymphoblastic Leukemia (ALL), Version 2.2015
5 secondary outcomes
Number of Participants With Adverse Events
Time frame: Up to about 8 months from start of study treatment.
Minimal Residual Disease (MRD) Negative CR/CRi Rate
Time frame: Up to about 8 months from start of treatment.
Overall Response Rate (ORR).
Time frame: Up to 8 months from start of treatment.
Overall Survival (OS).
Time frame: From the time of first study drug administration until date of death from any cause, assessed for up to about 15.6 months.
Proportion of Patients Bridged to Allogeneic Hematopoietic Cell Transplant (Allo-HCT or CAR-T.
Time frame: Time from start of treatment to date of hematopoietic cell transplant assessed for up to 8 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
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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.
Brian Jonas principal investigator
University of California, Davis
2 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 and Ibrutinib in people with Adult B Acute Lymphoblastic Leukemia and Philadelphia Chromosome Positive, run by University of California, Davis at 2 sites in United States.
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 12 inclusion and 22 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: finished, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
Yes. Results are posted in the registry (first posted 9 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Complete Remission (CR). (time frame: Up to about 3 months from start of study treatment.). 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 NCT02997761, 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 9 Jun 2026.