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

NCT03851081

Description:

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: I 66818
  • SECONDARY ID: NCI-2019-00565
  • SECONDARY ID: I 66818
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT03851081

Conditions

  • 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

Interventions

DrugSynonymsArms
Inotuzumab OzogamicinBesponsa, CMC-544, Way 207294, WAY-207294Treatment (inotuzumab ozogamicin, liposomal vincristine)
Vincristine Sulfate LiposomeMarqiboTreatment (inotuzumab ozogamicin, liposomal vincristine)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability of vincristine sulfate liposome (liposomal
      vincristine) and inotuzumab ozogamicin combination therapy in adult patients with relapsed
      and/or refractory B lineage acute lymphoblastic leukemia (B-ALL).

      II. To evaluate the overall response rate (ORR consisting of complete remission [CR],
      morphologic CR with incomplete blood count recovery [CRi], partial remission [PR],
      hematological improvement [HI]) of combination therapy with liposomal vincristine and
      inotuzumab ozogamicin in adult patients with relapsed and/or refractory B lineage acute
      lymphoblastic leukemia.

      SECONDARY OBJECTIVES:

      I. To evaluate the leukemia-free survival (LFS) and overall survival (OS) of patients treated
      with this combination.

      II. To evaluate the number of patients able to proceed onto subsequent hematopoietic stem
      cell transplantation (HSCT) following combination therapy following combination therapy.

      III. To evaluate the overall incidence of unique toxicities associated with these agents,
      specifically peripheral neuropathy following vincristine sulfate liposome and veno-occlusive
      disease of the liver (VOD) following inotuzumab ozogamicin therapy.

      EXPLORATORY OBJECTIVES:

      I. To explore minimal residual disease (MRD) as a potential correlative biomarker of response
      to combination vincristine sulfate liposome and inotuzumab ozogamicin therapy.

      II. To explore potential biomarkers of response to vincristine sulfate liposome and
      inotuzumab ozogamicin therapy.

      III. To perform an analysis of the estimated cost of outpatient administration of vincristine
      sulfate liposome and inotuzumab ozogamicin.

      IV. To evaluate quality of life (QOL) of patients with relapsed/refractory B-ALL treated with
      vincristine sulfate liposome and inotuzumab ozogamicin.

      OUTLINE: This is a phase Ib, dose-escalation study of inotuzumab ozogamicin followed by a
      phase II study.

      INDUCTION/RE-INDUCTION: Patients receive vincristine sulfate liposome intravenously (IV) over
      1 hour and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every
      28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
      Patients who achieve clinical benefit, defined as stable disease (SD), PR or CR, or CRi after
      1-2 cycles, will continue on to maintenance therapy for up to 4-5 cycles. Patients who do not
      achieve clinical benefit after cycle 1 but do not experience dose-limiting toxicities (DLTs)
      receive a second cycle of vincristine sulfate liposome and inotuzumab ozogamicin.

      MAINTENANCE: Patients receive vincristine sulfate liposome IV over 1 hour on days 1 and 15
      and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28
      days for up to 4-5 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 3
      months for up to 12 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (inotuzumab ozogamicin, liposomal vincristine)ExperimentalSee Detailed Description.
  • Inotuzumab Ozogamicin
  • Vincristine Sulfate Liposome

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicities (DLTs) (Phase Ib)
Time Frame:Up to 28 days
Safety Issue:
Description:The maximum dose level will be reached when 1 or fewer DLTs are observed in 6 patients.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Number of patients who proceed onto subsequent hematopoietic stem cell transplantation (HSCT)
Time Frame:Up to 12 months after last dose of study treatment
Safety Issue:
Description: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.
Measure:Number of patients who developed subsequent neurological toxicities and VOD
Time Frame:Up to 12 months after last dose of study treatment
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Roswell Park Cancer Institute

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