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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

Inotuzumab Ozogamicin and Blinatumomab With or Without Ponatinib in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia

A Phase II Study of Inotuzumab Ozogamicin Followed by Blinatumomab for Ph-Negative, CD22-Positive B-Lineage Acute Lymphoblastic Leukemia in Newly Diagnosed Older Adults or Adults With Relapsed or Refractory Disease

Inotuzumab Ozogamicin and Blinatumomab With or Without Ponatinib in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia (NCT03739814) is a Phase 2 interventional studying B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative and Recurrent B Acute Lymphoblastic Leukemia, sponsored by National Cancer Institute (NCI). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This phase II trial studies how well inotuzumab ozogamicin and blinatumomab with or without ponatinib work in treating patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed, has come back after a period of improvement (recurrent), or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug, called ozogamicin. Inotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD22 receptors, and delivers ozogamicin to kill them. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving inotuzumab ozogamicin and blinatumomab with or without ponatinib may be effective in treating patients with newly diagnosed, recurrent or refractory CD22 positive B-lineage acute lymphoblastic leukemia.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 84 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - STEP 0: Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory prior to registration; the bone marrow sample should be from the first aspiration (i.e. first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be initiated as soon as possible after pre-registration. The specimens should be sent to the HEME Biobank. - Lumbar Puncture (Spinal Tap) and Intrathecal Methotrexate: - Patients may receive the day 1 of course IA dose of intrathecal (IT) methotrexate during the prior-to-registration lumbar puncture (or the venous line placement) to avoid a second lumbar puncture. If the dose is administered prior to registration, then systemic chemotherapy must begin within 7 days of this IT chemotherapy. - STEP 1: Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on World Health Organization (WHO) criteria. Patients with Burkitt lymphoma/leukemia are not eligible. - STEP 1: CD22-positive disease defined as CD22 expression by \>= 20% of lymphoblasts by local hematopathology evaluation. - STEP 1: Philadelphia chromosome/BCR-ABL1-negative or Philadelphia chromosome/BCR-ABL1-positive B-cell ALL by cytogenetics, fluorescence in situ hybridization (FISH), and/or polymerase chain reaction (PCR). - STEP 1: No active central nervous system (CNS) leukemia (i.e. only CNS-1 disease allowed). Active CNS leukemia is defined as morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within 28 days prior to registration, symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurological dysfunction) within the 28 days prior to registration, and/or known asymptomatic parenchymal CNS mass lesions; see below for additional guidance. Prophylactic intrathecal medication alone is not an exclusion. - Categories of CNS Involvement for CNS Evaluation Prior to Registration: ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * STEP 0: Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory prior to registration; the bone marrow sample should be from the first aspiration (i.e. first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be initiated as soon as possible after pre-registration. The specimens should be sent to the HEME Biobank. * Lumbar Puncture (Spinal Tap) and Intrathecal Methotrexate: * Patients may receive the day 1 of course IA dose of intrathecal (IT) methotrexate during the prior-to-registration lumbar puncture (or the venous line placement) to avoid a second lumbar puncture. If the dose is administered prior to registration, then systemic chemotherapy must begin within 7 days of this IT chemotherapy. * STEP 1: Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on World Health Organization (WHO) criteria. Patients with Burkitt lymphoma/leukemia are not eligible. * STEP 1: CD22-positive disease defined as CD22 expression by \>= 20% of lymphoblasts by local hematopathology evaluation. * STEP 1: Philadelphia chromosome/BCR-ABL1-negative or Philadelphia chromosome/BCR-ABL1-positive B-cell ALL by cytogenetics, fluorescence in situ hybridization (FISH), and/or polymerase chain reaction (PCR). * STEP 1: No active central nervous system (CNS) leukemia (i.e. only CNS-1 disease allowed). Active CNS leukemia is defined as morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within 28 days prior to registration, symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurological dysfunction) within the 28 days prior to registration, and/or known asymptomatic parenchymal CNS mass lesions; see below for additional guidance. Prophylactic intrathecal medication alone is not an exclusion. * Categories of CNS Involvement for CNS Evaluation Prior to Registration: * CNS 1: CSF has \< 5 WBC/uL with cytospin negative for blasts; or \>= 10 red blood cell (RBC)/uL with cytospin negative for blasts. * CNS 2: CSF has \< 5 WBC/uL with cytospin positive for blasts; or \>= 10 RBC/uL with cytospin positive for blasts; or \>= 10 RBC/uL, WBC/uL \>= 5 but less than Steinherz/Bleyer algorithm with cytospin positive for blasts (see below). * CNS 3: CSF has \>= 5 WBC/uL with cytospin positive for blasts; or \>= 10 RBC/uL, \>= 5 WBC/uL and positive by Steinherz/Bleyer algorithm (see below); or clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome). Steinherz/Bleyer Method of Evaluating Initial Traumatic Lumbar Punctures: * If the patient has leukemia cells in the peripheral blood and the lumbar puncture is traumatic and contains \>= 5 WBC/uL with blasts, the following algorithm should be used to define CNS disease: CSF WBC/CSF RBC \> 2 x (Blood WBC/Blood RBC count) * STEP 1: Patients with known or suspected testicular involvement by leukemia are allowed provided that the patient receives concomitant scrotal/testicular radiotherapy. * Unilateral or bilateral testicular enlargement should be assessed by ultrasound or other imaging technique. Biopsy is recommended if clinical findings are equivocal or suggestive of hydrocele or a non-leukemic mass, but further assessments are per treating physician discretion. * STEP 1: Not pregnant and not nursing. * This study involves agents that have known genotoxic, mutagenic, and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required. * STEP 1: Eastern Cooperative Oncology Group (ECOG) performance status: 0-2 * STEP 1: No unstable cardiac disease such as myocardial infarction, angina pectoris, uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months of registration. * STEP 1: No impaired cardiac function, defined as left ventricular ejection fraction (LVEF) \< 45% or New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF). * STEP 1: Patients with known human immunodeficiency virus (HIV) infection are eligible if they have been on effective antiretroviral therapy with an undetectable viral load tested within 6 months of registration. * STEP 1: Patients with hepatitis B virus (HBV) are eligible only if they meet all the following: * On HBV-suppressive therapy. * No evidence of active virus. * No evidence of HBV-related liver damage. * STEP 1: Patients with hepatitis C virus (HCV) are eligible only if they meet all the following: * Successfully completed complete-eradication therapy with undetectable viral load. * No evidence of HCV-related liver damage. * STEP 1: No history of clinically relevant neurologic disorder such as epilepsy, seizure, aphasia, stroke, severe brain injury, structural brain abnormality, benign brain tumor, dementia, Parkinson's disease, movement disorder, cerebellar disease, or other significant CNS abnormalities. * STEP 1: No prior additional malignancy (i.e. in addition to ALL) except adequately treated basal- or squamous-cell skin cancer, in situ cervical cancer, stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for \>= 2 years. * STEP 1: No history of clinically significant ventricular arrhythmia, unexplained non-vasovagal syncope, or chronic bradycardic states such as sinoatrial block or higher degree of atrioventricular block unless a permanent pacemaker has been implanted. * STEP 1: No history of chronic liver disease, including cirrhosis. * STEP 1: No history of sinusoidal occlusion syndrome/veno-occlusive disease of the liver. * STEP 1: No uncontrolled infection or recent history (within 4 months prior to registration) of deep tissue infections such as fasciitis or osteomyelitis. * STEP 1: Total bilirubin, serum =\< 1.5 x upper limit of normal (ULN)\* * Except in the event of: 1) Gilbert disease, in which case total bilirubin must be =\< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to leukemic infiltration, in which case total bilirubin must be =\< 2 x ULN. * STEP 1: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN * STEP 1: Creatinine, serum =\< 1.5 ULN OR creatinine clearance \>= 40 mL/min * STEP 1: QT interval by Fridericia's correction formula (QTcF) =\< 470 msec * COHORT 1: Age \>= 60 years. * COHORT 1: Diagnosis of Philadelphia chromosome/BCR-ABL1-negative B-cell ALL. * COHORT 1: No prior treatment for ALL except a single dose of intrathecal chemotherapy, corticosteroids, hydroxyurea, and/or leukapheresis to reduce peripheral blast count and prevent ALL complications. Allowed therapy may be administered for no more than 14 days and must be completed \>= 24 hours prior to the initiation of protocol therapy. * COHORT 1: No plan for allogeneic or autologous hematopoietic cell transplantation (HCT). * COHORT 2: Age \>= 18 years. * COHORT 2: Diagnosis of Philadelphia chromosome/BCR-ABL1-negative B-cell ALL. * COHORT 2: Relapsed or refractory disease in salvage 1 or 2. * COHORT 2: No isolated extramedullary relapse. * COHORT 2: Prior allogeneic HCT permitted. * COHORT 2: Patients with prior allogeneic HCT must have completed transplantation \>= 4 months prior to registration. * COHORT 2: Patients with prior allogeneic HCT must have no evidence of graft-versus-host disease and must have completed immunosuppressive therapy \>= 30 days prior to registration. * COHORT 2: Prior treatment with inotuzumab ozogamicin, blinatumomab, other CD22-directed therapy, or other CD19-directed therapy is not allowed. * COHORT 2: Prior treatment with rituximab must be completed \>= 7 days prior to registration. * COHORT 2: Prior treatment with other monoclonal antibodies must be completed \>= 6 weeks prior to registration. * COHORT 2: Prior treatment for ALL must be completed \>= 14 days prior to registration with the following exceptions: intrathecal chemotherapy, hydroxyurea, corticosteroids, 6-mercaptopurine, methotrexate, vincristine, and/or leukapheresis to reduce circulating absolute lymphoblast count to =\< 10,000/uL or prevent complications related to ALL are allowed but must be completed \>= 24 hours prior to the initiation of protocol therapy. * COHORT 2: Patients should have resolution of any acute non-hematologic toxicities of prior therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 grade =\< 1. * COHORT 2: Peripheral blood absolute lymphoblast count =\< 10,000/uL (treatment allowed as above to reduce blast count to =\< 10,000/uL) * COHORT 3: Age ≥ 75 years OR age ≥ 18 years AND ineligible for hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HyperCVAD) regimens * COHORT 3: Diagnosis of Philadelphia chromosome/BCR-ABL1-positive B-cell ALL * COHORT 3: No prior treatment for ALL except a single dose of intrathecal chemotherapy, corticosteroids, hydroxyurea, BCR-ABL1-targeted tyrosine kinase inhibitor, and/or leukapheresis to reduce peripheral blast count and prevent ALL complications. Allowed non-protocol therapy may be administered for no more than 14 days and must be completed ≥ 24 hours prior to the initiation of protocol therapy. * COHORT 3: No chronic, strong CYP3A4 inducers

Treatments Being Tested

PROCEDURE

Biospecimen Collection

Undergo blood sample and cerebrospinal fluid collection

BIOLOGICAL

Blinatumomab

Given IV

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

BIOLOGICAL

Inotuzumab Ozogamicin

Given IV

PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

DRUG

Ponatinib

Given PO

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
Anchorage, Alaska, United States
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Anchorage Oncology Centre
Anchorage, Alaska, United States
Katmai Oncology Group
Anchorage, Alaska, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Kingman Regional Medical Center
Kingman, Arizona, United States
Mercy Hospital Fort Smith
Fort Smith, Arkansas, United States
PCR Oncology
Arroyo Grande, California, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States
Community Cancer Institute
Clovis, California, United States
University Oncology Associates
Clovis, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT03739814), the sponsor (National Cancer Institute (NCI)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT03739814 clinical trial studying?

This phase II trial studies how well inotuzumab ozogamicin and blinatumomab with or without ponatinib work in treating patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed, has come back after a period of improvement (recurrent), or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug, called ozogamicin. Inotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD22 receptors, and delivers ozo… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT03739814?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT03739814?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT03739814. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT03739814. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.