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Inotuzumab Ozogamicin and Vincristine Sulfate Liposome in Treating Patients With Relapsed or Refractory CD22+ B-cell Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT03851081
Recruitment Status : Not yet recruiting
First Posted : February 22, 2019
Last Update Posted : July 31, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
This phase Ib/II trial studies side effects and best dose of inotuzumab ozogamicin and how well it works when given together with vincristine sulfate liposome in treating patients with CD22 positive (+) B-cell acute lymphoblastic leukemia that has come back or dose not respond to treatment. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22+ cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as vincristine sulfate liposome, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving inotuzumab ozogamicin and vincristine sulfate liposome together may work better in treating patients with CD22+ B-cell acute lymphoblastic leukemia compared to giving inotuzumab ozogamicin or vincristine sulfate liposome alone.

Condition or disease Intervention/treatment Phase
Allogeneic Hematopoietic Stem Cell Transplantation Recipient Blasts 5 Percent or More of Bone Marrow Nucleated Cells Blasts 5 Percent or More of Peripheral Blood White Cells CD22 Positive Lymphoblasts 20 Percent or More of Bone Marrow Nucleated Cells Lymphoblasts 20 Percent or More of Peripheral Blood White Cells Recurrent B Acute Lymphoblastic Leukemia Refractory B Acute Lymphoblastic Leukemia Biological: Inotuzumab Ozogamicin Other: Quality-of-Life Assessment Drug: Vincristine Sulfate Liposome Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center, Open-Label Phase 1b/2 Study of Inotuzumab Ozogamicin and Vincristine Sulfate Liposome in Adult Patients With Relapsed/Refractory B Lineage Acute Lymphoblastic Leukemia (B-ALL)
Estimated Study Start Date : August 15, 2019
Estimated Primary Completion Date : December 12, 2021
Estimated Study Completion Date : December 12, 2022


Arm Intervention/treatment
Experimental: Treatment (inotuzumab ozogamicin, liposomal vincristine)
See Detailed Description.
Biological: Inotuzumab Ozogamicin
Given IV
Other Names:
  • Besponsa
  • CMC-544
  • Way 207294
  • WAY-207294

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Drug: Vincristine Sulfate Liposome
Given IV
Other Name: Marqibo




Primary Outcome Measures :
  1. Dose-limiting toxicities (DLTs) (Phase Ib) [ Time Frame: Up to 28 days ]
    The maximum dose level will be reached when 1 or fewer DLTs are observed in 6 patients.

  2. Overall response rate (ORR) (Phase II) [ Time Frame: Up to 12 months after last dose of study treatment ]
    Defined as complete remission (CR), morphologic CR with incomplete blood count recovery (CRi), partial remission (PR), hematological improvement (HI) based on modified International Working Group (IWG) criteria. Response is treated as a dichotomous variable and will be summarized by dose level using frequencies and relative frequencies. The ORR will be estimated using an 80% confidence interval obtained by Jeffrey?s prior method.

  3. Incidence of adverse events (AEs) [ Time Frame: Up to 12 months after last dose of study treatment ]
    Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4 and defined as the number of patients who received study combination who developed subsequent vascular occlusive disease (VOD) or neurological toxicities. The observed AEs and DLTs will be summarized by dose level and grade using frequencies and relative frequencies. AE and DLT rates will be estimated with 90% confidence intervals obtained using Jeffrey?s prior method.


Secondary Outcome Measures :
  1. Leukemia-free survival (LFS) [ Time Frame: Time from enrollment until disease progression/recurrence, death due to any cause, or last follow-up, assessed up to 12 months after last dose of study treatment ]
    Will be based on modified IWG criteria. Will be summarized by dose level using standard Kaplan-Meier methods. Estimates of the median LFS will be obtained with 90% confidence intervals.

  2. Overall survival [ Time Frame: Time from enrollment until death due to any cause or last follow-up, assessed up to 12 months after last dose of study treatment ]
    Will be based on modified IWG criteria. Will be summarized by dose level using standard Kaplan-Meier methods. Estimates of the median OS will be obtained with 90% confidence intervals.

  3. Number of patients who proceed onto subsequent hematopoietic stem cell transplantation (HSCT) [ Time Frame: Up to 12 months after last dose of study treatment ]
    The post-therapy HSCT status will be summarized by dose level using frequencies and relative frequencies. The HSCT rate will be estimated with 90% confidence intervals obtained using Jeffrey?s prior method.

  4. Number of patients who developed subsequent neurological toxicities and VOD [ Time Frame: Up to 12 months after last dose of study treatment ]
    The VOD and neurological toxicities will be summarized by dose level using frequencies and relative frequencies. The toxicity rates will be estimated with 90% confidence intervals obtained using Jeffrey?s prior method.


Other Outcome Measures:
  1. Minimal residual disease (MRD) after treatment [ Time Frame: Up to 12 months after last dose of study treatment ]
  2. Change in quality of life (QOL) [ Time Frame: Baseline up to 6 months ]
    Will be analyzed using the Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu).

  3. Estimated cost analysis for administration of treatment [ Time Frame: Up to 12 months after last dose of study treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group performance status between 0-2
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (Cockcroft and Gault) > 30 mL/min
  • Alanine aminotransferase (ALT) =< 5 x ULN
  • Direct bilirubin < 2.0 mg/dL
  • Left ventricular ejection fraction (LVEF) >= 40% as assessed by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan performed within 28 days of enrollment
  • Diagnosis of relapsed/refractory CD22+ B-cell ALL with disease in the bone marrow and/or peripheral blood by morphology (>=5% blasts). CD22-positive B-ALL is defined as expression by at least 20% of malignant lymphoblasts as determined by local flow cytometry and/or immunohistochemistry from a peripheral blood and/or bone marrow sample obtained within 2 weeks of screening
  • Relapsed or refractory disease, defined as first or greater bone marrow relapse from CR or overall response, specifically:

    • Any bone marrow relapse after allogeneic HSCT: subjects must be at least 1 month from HSCT at the time of screening and off immunosuppressive medication for at least 2 weeks at time of initial treatment (with the exception of low-dose steroids =< 20 mg prednisone equivalent) and have no active graft versus (vs.) host disease (GVHD);
    • Philadelphia chromosome (Ph) negative B-ALL which has not achieved CR or CRi after at least 1 attempt at remission induction using standard intensive chemotherapy regimen(s);
    • Philadelphia chromosome (Ph) positive B-cell ALL intolerant to or ineligible for BCR-ABL tyrosine kinase inhibitor (TKI) therapy or with disease which has progressed after at least two lines of prior TKI therapy
  • Participants of childbearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • Receipt of chemotherapy, radiotherapy, or investigational drug therapy within 2 weeks prior to treatment on study or those who have not recovered from adverse events due to agents administered > 2 weeks earlier
  • Active central nervous system involvement; patients who have a history of central nervous system (CNS) disease which has been effectively treated (as defined by at least one negative cerebrospinal sample prior to screening) are eligible
  • Prior malignancy, unless treated with curative intent and with no evidence of active disease present for > 5 years before screening, with the following exceptions:

    • Subjects with stage I breast cancer that has been completely and successfully treated, requiring no therapy or only anti-hormonal therapy
    • Subjects with T1N0M0 or T2N0M0 colorectal cancer who have been completely and successfully resected and who are disease-free for > 2 years prior to screening
    • Subjects with indolent prostate cancer, defined as clinical stage T1 or T2a, Gleason score =< 6, and prostate-specific antigen (PSA) < 10 ng/mL, requiring no therapy or only anti-hormonal therapy
    • Subjects with a history of basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, fully resected, and with no evidence of active disease
  • Uncontrolled intercurrent medical illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirements
  • Uncontrolled systemic fungal, bacterial, viral, or other infection defined as exhibiting ongoing signs and symptoms due to infection despite appropriate anti-infective therapy at time of screening
  • Pregnant or nursing female participants
  • Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
  • Presence of grade II-IV acute or extensive chronic graft versus host disease (GVHD) at time of screening
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator?s opinion deems the participant an unsuitable candidate to receive study drug including, but not limited to, medical, psychological, familial, social, or geographical considerations

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): NCT03851081


Locations
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United States, New York
Roswell Park Cancer Institute Not yet recruiting
Buffalo, New York, United States, 14263
Contact: Eunice S. Wang    716-845-3544    Eunice.wang@roswellpark.org   
Principal Investigator: Eunice S. Wang         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Eunice S Wang Roswell Park Cancer Institute

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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT03851081     History of Changes
Other Study ID Numbers: I 66818
NCI-2019-00565 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 66818 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
First Posted: February 22, 2019    Key Record Dates
Last Update Posted: July 31, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Burkitt Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Vincristine
Inotuzumab Ozogamicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action