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NCT03739814From ClinicalTrials.govRecruiting

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 inducers

What 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.

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Inotuzumab Ozogamicin and Blinatumomab With or Without Ponatinib in Treating Patients With Newly Diagnosed, Re | Trialion