RecruitingPhase 2

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 24 months, 3 years, 10 years
  • Procedures mentioned: Blood draws, Biopsies, Spinal tap (lumbar puncture)

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study."
  • "Patients undergo lumbar puncture with cerebrospinal fluid sample collection at baseline and may undergo additionally throughout the study."
  • "MAINTENANCE: Patients receive ponatinib PO QD for 24 months in the absence of disease progression or unacceptable toxicity."
  • "After completion of study treatment, patients are followed up every 3 months for 3 years, and then every 6 months for up to 10 years."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this 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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Official 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

Study sites (283)

AK

AL

AR

AZ

CA

DC

DE

FL

GA

  • Emory University Hospital/Winship Cancer Institute · Atlanta, GA 30322Site Public Contact · Study contact · 404-778-1868William G. Blum · Principal investigatorMore trials in Atlanta
  • Emory Saint Joseph's Hospital · Atlanta, GA 30342Site Public Contact · Study contact · 404-851-7115William G. Blum · Principal investigatorMore trials in Atlanta

IA

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic · Ankeny, IA 50023Site Public Contact · Study contact · 515-241-3305Seema Harichand-Herdt · Principal investigatorMore trials in Ankeny
  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic · Clive, IA 50325Site Public Contact · Study contact · 515-241-3305Seema Harichand-Herdt · Principal investigatorMore trials in Clive
  • UI Health Care Mission Cancer and Blood - Des Moines Clinic · Des Moines, IA 50309Site Public Contact · Study contact · 515-241-3305Seema Harichand-Herdt · Principal investigatorMore trials in Des Moines
  • UI Health Care Mission Cancer and Blood - Laurel Clinic · Des Moines, IA 50314Site Public Contact · Study contact · 515-241-3305Seema Harichand-Herdt · Principal investigatorMore trials in Des Moines
  • UI Health Care Mission Cancer and Blood - Waukee Clinic · Waukee, IA 50263Site Public Contact · Study contact · 515-241-3305Seema Harichand-Herdt · Principal investigatorMore trials in Waukee

ID

IL

KS

LA

MA

MD

MI

MN

MO

MT

NC

NE

NV

NY

OH

OK

OR

PA

VA

WA

WI

WV