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Trial record 1 of 1 for:    A041501
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Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT03150693
Recruitment Status : Recruiting
First Posted : May 12, 2017
Last Update Posted : May 8, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Study Description
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Brief Summary:
This partially randomized phase III trial studies the side effects of inotuzumab ozogamicin and how well it works when given with frontline chemotherapy in treating patients with newly diagnosed B acute lymphoblastic leukemia. Monoclonal antibodies, such as inotuzumab ozogamicin, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving inotuzumab ozogamicin with chemotherapy may work better in treating young adults with B acute lymphoblastic leukemia.

Condition or disease Intervention/treatment Phase
B Acute Lymphoblastic Leukemia Drug: Allopurinol Drug: Cytarabine Drug: Daunorubicin Hydrochloride Drug: Vincristine Sulfate Drug: Dexamethasone Drug: Pegylated L-Asparaginase Drug: Methotrexate Procedure: Bone Marrow Aspiration and Biopsy Drug: Cyclophosphamide Drug: Mercaptopurine Biological: Rituximab Drug: Doxorubicin Drug: Thioguanine Biological: Inotuzumab Ozogamicin Other: Laboratory Biomarker Analysis Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Trial to Evaluate the Efficacy of the Addition of Inotuzumab Ozogamicin (a Conjugated Anti-CD22 Monoclonal Antibody) to Frontline Therapy in Young Adults (Ages 18-39 Years) With Newly Diagnosed Precursor B-Cell ALL
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : August 2024

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Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm I (frontline chemotherapy)
See detailed description.
 Drug: Allopurinol
Given PO

Drug: Cytarabine
Given IT, IV, SC

Drug: Daunorubicin Hydrochloride
Given IV

Drug: Vincristine Sulfate
Given IV

Drug: Dexamethasone
Given PO or IV

Drug: Pegylated L-Asparaginase
Given IV

Drug: Methotrexate
Given IT, IV, PO

Procedure: Bone Marrow Aspiration and Biopsy
Undergo bone marrow aspiration and biopsy

Drug: Cyclophosphamide
Given IV

Drug: Mercaptopurine
Given PO

Biological: Rituximab
Given IV

Drug: Thioguanine
Given PO

Other: Laboratory Biomarker Analysis
Correlative studies
Experimental: Arm II (frontline chemotherapy, inotuzumab ozogamicin)
Patients receive inotuzumab ozogamicin IV on days 1, 8, and 15 and undergo bone marrow aspirate and biopsy on day 28. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive remission consolidated chemotherapy, interim maintenance chemotherapy, delayed intensification, and maintenance therapy as in Arm I.
 Drug: Allopurinol
Given PO

Drug: Cytarabine
Given IT, IV, SC

Drug: Daunorubicin Hydrochloride
Given IV

Drug: Vincristine Sulfate
Given IV

Drug: Dexamethasone
Given PO or IV

Drug: Pegylated L-Asparaginase
Given IV

Drug: Methotrexate
Given IT, IV, PO

Procedure: Bone Marrow Aspiration and Biopsy
Undergo bone marrow aspiration and biopsy

Drug: Cyclophosphamide
Given IV

Drug: Mercaptopurine
Given PO

Biological: Rituximab
Given IV

Drug: Doxorubicin
Given IV

Drug: Thioguanine
Given PO

Biological: Inotuzumab Ozogamicin
Given IV

Other: Laboratory Biomarker Analysis
Correlative studies


Outcome Measures
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Primary Outcome Measures :
  1. EFS [ Time Frame: Time from induction response to the time of progressive-disease, secondary malignancy, or death, assessed up to 3 years ]
    Will be compared using log-rank tests. EFS curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. The corresponding hazard ratio, 2- and 3-year EFS estimates will be assessed, and EFS medians along with their 95% confidence intervals for the two treatment arms.


Secondary Outcome Measures :
  1. DFS [ Time Frame: Time from achievement of CR to the time of relapse and/or death, assessed up to 10 years ]
  2. OS [ Time Frame: Time from randomization to the time of death due to any cause, assessed up to 10 years ]
    Will be evaluated using Kaplan-Meier as well as Cox regression models.

  3. Proportion of patients who achieve CR or any response to induction therapy [ Time Frame: Up to 10 years ]
    Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.

  4. Overall induction response rates [ Time Frame: Up to 10 years ]
    Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.

  5. Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ]
    The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms. Tolerability of the treatment arms will be assessed through assessing the number of patients who required dose modifications and/or dose delays.

  6. Proportion of patients who go off treatment due to adverse reactions [ Time Frame: Up to 10 years ]
    Will be assessed within each of the treatment arms and differences explores in these measures between the arms.

  7. Proportion of patients who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial [ Time Frame: Up to 10 years ]
    Will be assessed within each of the treatment arms and differences explores in these measures between the arms.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 39 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

REGISTRATION ELIGIBILITY CRITERIA (STEP 1)

  • Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia (WHO criteria) are eligible. Patients with Burkitt type ALL are NOT eligible
  • Patients who have BCR-ABL fusion transcript determined by fluorescence in situ hybridization (FISH) or real time-polymerase chain reaction (RT-PCR) or t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for enrollment on studies that incorporate imatinib during induction; please note: flow cytometry is to be performed at the local reference lab and must include assessment of CD20 and CD22 positivity, as well as CD29 and CD22 anti-positivity
  • No prior therapy except for limited treatment (< 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine
  • No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys; when indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC
  • Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systematic therapy for patient convenience; systemic chemotherapy must begin within 72 hours of this intrathecal therapy
  • Patients receiving prior steroid therapy are eligible for study; the dose and duration of previous steroid therapy should be carefully documented on case report forms
  • Not pregnant and not nursing; for women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patients with down syndrome are excluded from this study
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN), unless suspected leukemic involvement of the liver
  • Direct bilirubin =< 3 x upper limit of normal (ULN), unless suspected leukemic involvement of the liver
  • Calculated (calc.) creatinine clearance >= 50 mL/min by Cockcroft-Gault

RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2)

  • Completion of remission induction therapy

  • Patients with M2 marrow or better are eligible; patients with M3 or M4 marrow (greater than 25% lymphoblasts) will not be eligible to be randomized

    • Rating: M0, M1; Blast Cells (%): 0-5.0
    • Rating: M2; Blast Cells (%): 5.1-25.0
    • Rating: M3; Blast Cells (%): > 25-50
    • Rating: M4; Blast Cells (%): > 50.0
    • The term "blast cell" includes any cell that cannot be classified as a more mature normal element, and includes "leukemic cells," pathologic lymphocytes, and stem cells
  • No ascites, effusions or significant edema
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin =< 1.5 x upper limit of normal (ULN), except for patients with known Gilbert's syndrome
  • Aspartate aminotransferase (AST) =< 8 x upper limit of normal (ULN)
  • Completion of first 12 weeks (12+ weeks) of maintenance therapy (Course V)
  • Patient has at least 24 weeks (24+ weeks) remaining before end of maintenance therapy (Course V)
  • Patient is in complete continuous first remission at entry into A041501-HO1
  • Patient is receiving oral anti-metabolite chemotherapy during the maintenance phase of therapy; treatment plan must call for the following doses of antimetabolites: 6MP 75 mg/m2/day orally; methotrexate (MTX) 20 mg/m2/week orally (modification of 6 MP or MTX dosing based on laboratory or clinical parameters is acceptable)
  • Patient is able and willing to use the Medication Event Monitoring System (MEMS) TrackCap (e.g. not using a pillbox)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03150693


Contacts
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Contact: Daniel J. DeAngelo, MD, PhD 617-632-2645 daniel_deangelo@dfci.harvard.edu

Locations
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Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
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Study Chair: daniel_deangelo@dfci.harvard.edu J. DeAngelo, MD, PhD Dana-Farber Cancer Institute
More Information
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Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT03150693    
Other Study ID Numbers: A041501
NCI-2016-01981 ( Registry Identifier: Clinical Trial Reporting Program )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: May 12, 2017    Key Record Dates
Last Update Posted: May 8, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Cyclophosphamide
Rituximab
Doxorubicin
Methotrexate
 Vincristine
Daunorubicin
Asparaginase
Mercaptopurine
Thioguanine
Inotuzumab Ozogamicin
Pegaspargase
Allopurinol
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action