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

RecruitingPhase 2

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

Who can join

Ages 18 and older · All sexes

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

About the study

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 is being tested

Sponsor: National Cancer Institute (NCI) · Participants: 84 · Started: May 8, 2019

Contact the study team

Official record on ClinicalTrials.gov — NCT03739814

Locations in the U.S.

CaliforniaCity of Hope Comprehensive Cancer Center, Duarte
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care, Irvine
UC San Diego Moores Cancer Center, La Jolla
UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange
DelawareHelen F Graham Cancer Center, Newark
Medical Oncology Hematology Consultants PA, Newark
District of ColumbiaMedStar Georgetown University Hospital, Washington D.C.
FloridaJupiter Medical Center, Jupiter
GeorgiaEmory Saint Joseph's Hospital, Atlanta
Emory University Hospital/Winship Cancer Institute, Atlanta
IdahoSaint Alphonsus Cancer Care Center-Nampa, Nampa
IllinoisNorthwestern University, Chicago
University of Chicago Comprehensive Cancer Center, Chicago
University of Illinois, Chicago
Cancer Care Specialists of Illinois - Decatur, Decatur
Crossroads Cancer Center, Effingham
NorthShore University HealthSystem-Evanston Hospital, Evanston
NorthShore University HealthSystem-Glenbrook Hospital, Glenview
NorthShore University HealthSystem-Highland Park Hospital, Highland Park
Loyola University Medical Center, Maywood
UC Comprehensive Cancer Center at Silver Cross, New Lenox
University of Chicago Medicine-Orland Park, Orland Park
Illinois CancerCare-Peoria, Peoria
KansasUniversity of Kansas Cancer Center, Kansas City
University of Kansas Hospital-Westwood Cancer Center, Westwood
MichiganTrinity Health Saint Joseph Mercy Hospital Ann Arbor, Ann Arbor
Trinity Health IHA Medical Group Hematology Oncology - Brighton, Brighton
Trinity Health Medical Center - Brighton, Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton, Canton
Trinity Health Medical Center - Canton, Canton
Chelsea Hospital, Chelsea
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital, Chelsea
Henry Ford Health Saint John Hospital, Detroit
Henry Ford River District Hospital, East China Township
Cancer Hematology Centers - Flint, Flint
Genesys Hurley Cancer Institute, Flint
Hurley Medical Center, Flint
Henry Ford Saint John Hospital - Academic, Grosse Pointe Woods
Henry Ford Saint John Hospital - Van Elslander, Grosse Pointe Woods
Trinity Health Saint Mary Mercy Livonia Hospital, Livonia
Henry Ford Saint John Hospital - Macomb Medical, Macomb
Trinity Health Saint Joseph Mercy Oakland Hospital, Pontiac
MyMichigan Medical Center Saginaw, Saginaw
MyMichigan Medical Center Tawas, Tawas City
Henry Ford Health Warren Hospital, Warren
Henry Ford Warren Hospital - GLCMS, Warren
Huron Gastroenterology PC, Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus, Ypsilanti
MissouriSiteman Cancer Center at Saint Peters Hospital, City of Saint Peters
Siteman Cancer Center at West County Hospital, Creve Coeur
Mercy Hospital Saint Louis, St Louis
Mercy Hospital South, St Louis
Siteman Cancer Center at Christian Hospital, St Louis
Siteman Cancer Center-South County, St Louis
Washington University School of Medicine, St Louis
NevadaOptumCare Cancer Care at Charleston, Las Vegas
OptumCare Cancer Care at Fort Apache, Las Vegas
New YorkNorthwell Health/Center for Advanced Medicine, Lake Success
North Shore University Hospital, Manhasset
Long Island Jewish Medical Center, New Hyde Park
University of Rochester, Rochester
Stony Brook University Medical Center, Stony Brook
North CarolinaWake Forest University Health Sciences, Winston-Salem
OhioUniversity of Cincinnati Cancer Center-UC Medical Center, Cincinnati
Ohio State University Comprehensive Cancer Center, Columbus
University of Cincinnati Cancer Center-West Chester, West Chester
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
OregonProvidence Portland Medical Center, Portland
Providence Saint Vincent Medical Center, Portland
VirginiaVCU Massey Comprehensive Cancer Center, Richmond
West VirginiaWest Virginia University Healthcare, Morgantown
WisconsinMarshfield Medical Center-EC Cancer Center, Eau Claire
Marshfield Medical Center-Marshfield, Marshfield
Froedtert Menomonee Falls Hospital, Menomonee Falls
Medical College of Wisconsin, Milwaukee
Marshfield Medical Center - Minocqua, Minocqua
Froedtert and MCW Moorland Reserve Health Center, New Berlin
Drexel Town Square Health Center, Oak Creek
Marshfield Medical Center-Rice Lake, Rice Lake
Marshfield Medical Center-River Region at Stevens Point, Stevens Point
Froedtert West Bend Hospital/Kraemer Cancer Center, West Bend
Marshfield Medical Center - Weston, Weston

Conditions

From ClinicalTrials.gov, data retrieved Oct 2, 2026. Each study sets its own eligibility; the study team decides who can join.