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

NCT03851081 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: I 66818NCI-2019-00565
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicities (DLTs) (Phase Ib)

  The maximum dose level will be reached when 1 or fewer DLTs are observed in 6 patients.

  Up to 28 days

• Overall response rate (ORR) (Phase II)

  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.

  Up to 12 months after last dose of study treatment

• Incidence of adverse events (AEs)

  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.

  Up to 12 months after last dose of study treatment

Secondary Outcomes (4)

• Leukemia-free survival (LFS)

  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

• Overall survival

  Time from enrollment until death due to any cause or last follow-up, assessed up to 12 months after last dose of study treatment

• Number of patients who proceed onto subsequent hematopoietic stem cell transplantation (HSCT)

  Up to 12 months after last dose of study treatment

• Number of patients who developed subsequent neurological toxicities and VOD

  Up to 12 months after last dose of study treatment

Other Outcomes (3)

• Minimal residual disease (MRD) after treatment

  Up to 12 months after last dose of study treatment

• Change in quality of life (QOL)

  Baseline up to 6 months

• Estimated cost analysis for administration of treatment

  Up to 12 months after last dose of study treatment

Study Arms (1)

Treatment (inotuzumab ozogamicin, liposomal vincristine)

EXPERIMENTAL

See Detailed Description.

Biological: Inotuzumab Ozogamicin; Other: Quality-of-Life Assessment; Drug: Vincristine Sulfate Liposome

Interventions

Inotuzumab Ozogamicin BIOLOGICAL

Given IV

Also known as: Besponsa, CMC-544, Way 207294, WAY-207294

Treatment (inotuzumab ozogamicin, liposomal vincristine)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (inotuzumab ozogamicin, liposomal vincristine)

Vincristine Sulfate Liposome DRUG

Given IV

Also known as: Marqibo

Treatment (inotuzumab ozogamicin, liposomal vincristine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Total bilirubin= \< 1.5 x ULN
• 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 second or greater bone marrow relapse from CR or overall response or, disease has progressed following two or more anti-leukemia therapies. 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 2 attempts 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 and for females, at least 8 months after the final dose of inotuzumab ozogamicin. Males with female partners of childbearing potential must agree to use adequate contraceptive prior to study entry and for at least 5 months after the final dose of inotuzumab ozogamicin. 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 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

You may not qualify if:

• 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
• Participants on oral or injectable calcineurin inhibitors (e.g., cyclosporin, tacrolimus) within 4 weeks prior to study enrollment
• 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
• Known active hepatitis B, known 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Pfizer: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

Inotuzumab Ozogamicin; Vincristine

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Eunice S Wang

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 22, 2019
• Study Start: January 21, 2021
• Primary Completion: January 21, 2023
• Study Completion: January 21, 2024
• Last Updated: January 28, 2022

Record last verified: 2022-01

Locations

US (1)