NCI ID NCI-2018-02484
NCT ID NCT03739814
CTEP ID A041703
Primary Purpose TREATMENT
Anatomic Sites Lymphoid Leukemia
Minimum Age 18 Years
Maximum Age 999 Years
Gender BOTH
Lead Org Alliance for Clinical Trials in Oncology
Principal Investigator Matthew Joseph Wieduwilt
NCI Site View on ClinicalTrials.gov

Inotuzumab Ozogamicin and Blinatumomab in Treating Patients with Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia

This phase II trial studies how well inotuzumab ozogamicin and blinatumomab work in treating patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed, has come back, or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and blinatumomab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Eligibility

Inclusion Criterea

  • Pre-registration Eligibility 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.
  • Registration Eligibility Criteria (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.
  • CD22-positive disease defined as CD22 expression by >= 20% of lymphoblasts by local hematopathology evaluation.
  • Philadelphia chromosome/BCR-ABL1-negative ALL by cytogenetics, fluorescence in situ hybridization (FISH), and/or polymerase chain reaction (PCR). If any test is positive for Philadelphia chromosome/BCR-ABL1, then the patient is ineligible.
  • 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)
  • 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.
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
  • No unstable cardiac disease such as myocardial infarction, angina pectoris, uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months of registration.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • No history of chronic liver disease, including cirrhosis.
  • No history of sinusoidal occlusion syndrome/veno-occlusive disease of the liver.
  • No uncontrolled infection or recent history (within 4 months prior to registration) of deep tissue infections such as fasciitis or osteomyelitis.
  • 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.
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine, serum =< 1.5 ULN OR creatinine clearance >= 40 mL/min
  • QT interval by Fridericia's correction formula (QTcF) =< 470 msec
  • Cohort 1 Patients Only
  • Age >= 60 years.
  • 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.
  • No plan for allogeneic or autologous hematopoietic cell transplantation (HCT).
  • Cohort 2 Patients Only:
  • Age >= 18 years.
  • Relapsed or refractory disease in salvage 1 or 2.
  • No isolated extramedullary relapse.
  • Prior allogeneic HCT permitted.
  • Patients with prior allogeneic HCT must have completed transplantation >= 4 months prior to registration.
  • 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.
  • Prior treatment with inotuzumab ozogamicin, blinatumomab, other CD22-directed therapy, or other CD19-directed therapy is not allowed.
  • Prior treatment with rituximab must be completed >= 7 days prior to registration.
  • Prior treatment with other monoclonal antibodies must be completed >= 6 weeks prior to registration.
  • 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.
  • 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.
  • Peripheral blood absolute lymphoblast count =< 10,000/uL (treatment allowed as above to reduce blast count to =< 10,000/uL)

Exclusion Criterea


Participating Clinics

University Medical Center of Southern Nevada


1800 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Central Valley


3730 South Eastern Avenue
Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Henderson


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Alliance for Childhood Diseases/Cure 4 the Kids Foundation


One Breakthrough Way
Las Vegas, NV 89135
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada


9280 West Sunset Road
Suite 100 Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

Radiation Oncology Associates


6630 B South McCarran
Suite 18 Reno, NV 89509
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Central


624 South Tonopah Drive
Las Vegas, NV 89106
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Northwest


7445 Peak Drive
Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Carson Tahoe Regional Medical Center


1535 Medical Parkway
Pharmacy Suite C Carson City, NV 89703
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Henderson


10001 South Eastern Avenue
Suite 108 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Tenaya


2851 North Tenaya Way
Suite 101 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Las Vegas


3006 South Maryland Parkway
Suite 100 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Henderson


52 North Pecos Road
Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Henderson


2904 West Horizon Ridge Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Southeast Henderson


1505 Wigwam Parkway
Suite 130 Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Medical Center


6450 Medical Center Street
Las Vegas, NV 89148-2405
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Southeast


3980 South Eastern Avenue
Las Vegas, NV 89119
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Fort Apache


6160 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Vegas Tenaya


2851 North Tenaya Way
Suite 100 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Fort Apache


6190 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-San Martin


8285 West Arby Avenue
Suite 100 Las Vegas, NV 89113
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills


6850 North Durango Drive
Suite 120 Las Vegas, NV 89149
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Summerlin


655 North Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Summerlin Hospital Medical Center


657 Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Ann M Wierman MD LTD


3150 Tenaya Way
Suite 200 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Horizon Ridge


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at MountainView


3150 North Tenaya Way
Suite 510 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Kingman Regional Medical Center


3269 Stockton Hill Road
Kingman, AZ 86401
Map

702-384-0013
research@sncrf.org

University Cancer Center


3131 La Canada Street
Suite 231 Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada


6827 West Tropicana Avenue
Suite 110 Las Vegas, NV 89103
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Charleston


2300 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013

Desert West Surgery


1111 Shadow Lane
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada-Pahrump


2340 East Calvada Boulevard
Suite 7 Pahrump, NV 89048
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Seven Hills


3175 Saint Rose Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Town Center


653 North Town Center Drive
Suite 402 Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

PCR Oncology


584 Camino Mercado
Arroyo Grande, CA 93420
Map

702-384-0013
research@sncrf.org

Sunrise Hospital and Medical Center


3186 South Maryland Parkway
Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

Renown Regional Medical Center


1155 Mill Street
Reno, NV 89502
Map

702-384-0013
research@sncrf.org

Saint Mary's Regional Medical Center


235 West Sixth Street
Reno, NV 89503
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway


3006 South Maryland Parkway
Suite 205 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

Urology Specialists of Nevada - Southwest


8410 West Warm Springs Road
Suite 10 Las Vegas, NV 89113
Map


research@sncrf.org

Las Vegas Urology - Sunset


7150 West Sunset Road
Suite 201A and 202B Las Vegas, NV 89113
Map


research@sncrf.org

Las Vegas Prostate Cancer Center


7150 West Sunset Road
Suite 100 Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Northwest


3150 North Tenaya Way
Suite 165 Las Vegas, NV 89128
Map


research@sncrf.org

Las Vegas Urology - Cathedral Rock


7200 Cathedral Rock Drive
Suites 180 and 210 Las Vegas, NV 89128
Map


research@sncrf.org

Las Vegas Urology - Pebble


8915 South Pecos Road
Suite 19A Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Pecos


9053 South Pecos Road
Suite 2900 Las Vegas, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Green Valley


1701 North Green Valley Parkway
Suite 10C Henderson, NV 89074
Map


research@sncrf.org

Urology Specialists of Nevada - Green Valley


58 North Pecos Road
Henderson, NV 89074
Map


research@sncrf.org

Urology Specialists of Nevada - Central


2010 Wellness Way
Suite 200 Las Vegas, NV 89106
Map


research@sncrf.org

Valley Medical Center


400 South 43rd Street
Renton, WA 98055
Map

425-228-3440
research@valleymed.org