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
- B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative
- Recurrent B Acute Lymphoblastic Leukemia
- Refractory B Acute Lymphoblastic Leukemia
At a glance
- Phase
- Phase 2
- Study type
- Interventional
- Sponsor
- National Cancer Institute (NCI)
- Enrolment target
- 84
- Started
- 8 May 2019
- Main results due
- 1 February 2027
- Study sites
- 280
- Registry updated
- 29 September 2026
Can you take part?
- Aged 18 years and over.
- Open to any sex.
- You need the condition being studied — healthy volunteers are not accepted.
These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.
Read the full eligibility criteria
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 inducersWhat this study is about
In the sponsor’s own words, from the registry.
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.
Study sites(280)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Active, not recruiting
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, United States
Suspended
Anchorage Radiation Therapy Center
Anchorage, Alaska, United States
Suspended
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Suspended
Alaska Oncology and Hematology LLC
Anchorage, Alaska, United States
Suspended
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Suspended
Anchorage Oncology Centre
Anchorage, Alaska, United States
Suspended
Katmai Oncology Group
Anchorage, Alaska, United States
Suspended
Providence Alaska Medical Center
Anchorage, Alaska, United States
Suspended
Kingman Regional Medical Center
Kingman, Arizona, United States
Suspended
Mercy Hospital Fort Smith
Fort Smith, Arkansas, United States
Suspended
PCR Oncology
Arroyo Grande, California, United States
Suspended
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States
Suspended
Community Cancer Institute
Clovis, California, United States
Active, not recruiting
University Oncology Associates
Clovis, California, United States
Active, not recruiting
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, United States
Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
Recruiting
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Active, not recruiting
Beebe Medical Center
Lewes, Delaware, United States
Suspended
Beebe South Coastal Health Campus
Millville, Delaware, United States
Suspended
Delaware Clinical and Laboratory Physicians PA
Newark, Delaware, United States
Suspended
Helen F Graham Cancer Center
Newark, Delaware, United States
Recruiting
Medical Oncology Hematology Consultants PA
Newark, Delaware, United States
Recruiting
Christiana Care Health System-Christiana Hospital
Newark, Delaware, United States
Suspended
Beebe Health Campus
Rehoboth Beach, Delaware, United States
Suspended
TidalHealth Nanticoke / Allen Cancer Center
Seaford, Delaware, United States
Suspended
Christiana Care Health System-Wilmington Hospital
Wilmington, Delaware, United States
Suspended
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Recruiting
Holy Cross Hospital
Fort Lauderdale, Florida, United States
Suspended
Jupiter Medical Center
Jupiter, Florida, United States
Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Recruiting
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States
Recruiting
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Suspended
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, United States
Suspended
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, United States
Suspended
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, United States
Recruiting
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, United States
Suspended
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, United States
Suspended
OSF Saint Anthony's Health Center
Alton, Illinois, United States
Suspended
Illinois CancerCare-Bloomington
Bloomington, Illinois, United States
Suspended
Loyola Center for Health at Burr Ridge
Burr Ridge, Illinois, United States
Suspended
Illinois CancerCare-Canton
Canton, Illinois, United States
Suspended
Memorial Hospital of Carbondale
Carbondale, Illinois, United States
Suspended
SIH Cancer Institute
Carterville, Illinois, United States
Suspended
Illinois CancerCare-Carthage
Carthage, Illinois, United States
Suspended
Centralia Oncology Clinic
Centralia, Illinois, United States
Suspended
Northwestern University
Chicago, Illinois, United States
Recruiting
University of Illinois
Chicago, Illinois, United States
Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Recruiting
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States
Recruiting
Decatur Memorial Hospital
Decatur, Illinois, United States
Suspended
Illinois CancerCare-Dixon
Dixon, Illinois, United States
Suspended
Crossroads Cancer Center
Effingham, Illinois, United States
Recruiting
Illinois CancerCare-Eureka
Eureka, Illinois, United States
Suspended
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States
Recruiting
Illinois CancerCare-Galesburg
Galesburg, Illinois, United States
Suspended
Western Illinois Cancer Treatment Center
Galesburg, Illinois, United States
Suspended
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, United States
Recruiting
Showing 60 of 280 sites — filter to narrow it down. 84 of the 280 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.
Source: ClinicalTrials.gov record NCT03739814. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.
Not the right study?
Answer three questions and see the studies recruiting near you, in plain language.
Find a study for me