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Inotuzumab Ozogamicin in Treating Patients with Acute Lymphocytic Leukemia and Non-Hodgkin's Lymphoma after Transplant

Trial Status: Active

This phase I / II trial studies the side effects and best dose of inotuzumab ozogamicin and how well it works in treating patients with acute lymphocytic leukemia and Non-Hodgkin's lymphoma after transplant. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent, called CalichDMH. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers CalichDMH to kill them.

Inclusion Criteria

  • PHASE I ALL: Diagnosis of CD22-positive acute lymphoblastic leukemia
  • PHASE I ALL: Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • PHASE I ALL: Patients who are between T+40 and T+100 after allogeneic transplantation; patients must receive their first dose of inotuzumab at or before T+100
  • PHASE I ALL: Patients who have/are either: * Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation ** Pre- or post-transplant minimal residual disease defined by: *** Any detectable acute lymphocytic leukemia (ALL) (by flow cytometry, cytogenetics, or polymerase chain reaction [PCR] techniques) as per clinical indication * In second or third complete remission at the time of allogeneic transplantation * Treated with reduced intensity regimens or non-myeloablative conditioning regimens * Lymphoid blast crisis of chronic myelogenous leukemia (CML) * Are relapsed or refractory to at least 1 line of chemotherapy * Philadelphia-like ALL
  • PHASE I ALL: Patients who have evidence of donor chimerism after allogeneic transplantation
  • PHASE I ALL: Eastern Cooperative Oncology Group (ECOG) performance status =-< 2
  • PHASE I ALL: Subjects must have absolute neutrophil count (ANC) > 1,000 for 3 days and platelet transfusion independence as defined as a platelet count > 50,000 for 7 days
  • PHASE I ALL: Able to adhere to the study visit schedule and other protocol requirements
  • PHASE I ALL: Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • PHASE I NHL: Diagnosis of CD22-positive B-cell Non-Hodgkin’s Lymphoma * Patients with 1) Diffuse large B cell lymphoma; 2) Transformed indolent lymphoma; 3) Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with Richter’s transformation and 4) High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements. Patients must have received an autologous hematopoietic stem cell transplant under one of the following conditions: ** Achieved partial remission (defined as Deauville 4 on positron emission tomography [PET]/computed tomography [CT]) after treatment with platinum – containing salvage regimen; ** Failed first platinum – containing salvage regimen and achieved complete or partial remission after two separate lines of platinum – containing regimen; ** Had a second autologous hematopoietic stem cell transplant after achieving complete or partial remission with the first autologous transplant; or ** Had relapsed or refractory disease involving the bone marrow prior to receiving salvage therapy
  • PHASE I NHL: The patient’s lymphoma must be CD22 positive either by immunohistochemistry or flow cytometry analysis
  • PHASE I NHL: Patients who are between T+40 and T+100 after autologous transplantation. Patients must receive their first dose of inotuzumab at or before T+100
  • PHASE I NHL: ECOG performance status =< 2
  • PHASE I NHL: Subjects must have ANC > 1,000/uL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/uL for 7 days
  • PHASE I NHL: Able to adhere to the study visit schedule and other protocol requirements
  • PHASE I NHL: Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • PHASE II ALL: Diagnosis of CD22-positive acute lymphoblastic leukemia
  • PHASE II ALL: Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • PHASE II ALL: Patients who are between T+40 and T+100 after allogeneic transplantation
  • PHASE II ALL: Patients who have/are either: * Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation ** Post-Transplant Minimal Residual Disease defined by: *** Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication * In second or third complete remission at the time of allogeneic transplantation * Treated with reduced intensity regimens as defined per institutional standard of practice * Lymphoid blast crisis of CML * Are relapsed or refractory to at least 1 line of chemotherapy * Philadelphia-like ALL
  • PHASE II ALL: Patients who have >= 80% donor chimerism after allogeneic transplantation
  • PHASE II ALL: Philadelphia chromosome positive ALL must have failed at least 1 TKI
  • PHASE II ALL: ECOG performance status =< 1
  • PHASE II ALL: Subjects must have ANC > 1,000/uL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/uL for 7 days
  • PHASE II ALL: Able to adhere to the study visit schedule and other protocol requirements
  • PHASE II ALL: Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • PHASE II NHL: Patients with 1) Diffuse large B cell lymphoma; 2) Transformed indolent lymphoma; 3) CLL/SLL with Richter’s transformation and 4) High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements. Patients must have received an autologous hematopoietic stem cell transplant under one of the following conditions: * Achieved partial remission (defined as Deauville 4 on PET/CT)after treatment with platinum – containing salvage regimen; * Failed first platinum – containing salvage regimen and achieved complete or partial remission after two separate lines of platinum – containing regimen; * Had a second autologous hematopoietic stem cell transplant after achieving complete or partial remission with the first autologous transplant; or * Had relapsed or refractory disease involving the bone marrow prior to receiving salvage therapy
  • PHASE II NHL: The patient’s lymphoma must be CD22 positive either by immunohistochemistry or flow cytometry analysis
  • PHASE II NHL: Patients who are between T+40 and T+100 after autologous transplantation. Patients must receive their first dose of inotuzumab at or before T+100
  • PHASE II NHL: ECOG performance status =< 1
  • PHASE II NHL: Subjects must have ANC > 1,000/uL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/uL for 7 days
  • PHASE II NHL: Able to adhere to the study visit schedule and other protocol requirements
  • PHASE II NHL: Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Patients with clinical evidence of disease progression prior to enrollment
  • Persistent prior treatment toxicities grade 2 and above according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (with the exception for alopecia, neuropathy, etc.)
  • For patients with NHL: Active central nervous system or meningeal involvement by lymphoma. Patients with a history of central nervous system (CNS) or meningeal involvement must be in a documented remission. For patients with ALL: active central nervous system involvement with ALL
  • Creatinine clearance < 30 ml/min
  • Bilirubin >= 2 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) >= 2 X institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) >= 2 X institutional upper limit of normal
  • Graft versus host disease (GVHD) grade III or IV (for patients with a prior allogeneic transplant)
  • Active acute or chronic GVHD of the liver (for patients with a prior allogeneic transplant)
  • History of veno-occlusive disease (VOD)
  • Active malignancy
  • Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breastfeeding women are excluded from this study because inotuzumab ozogamicin may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with inotuzumab ozogamicin, breastfeeding should be discontinued if the mother is treated with inotuzumab ozogamicin. These potential risks may also apply to other agents used in this study
  • Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
  • Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
  • Participation in any other investigational drug study or had exposure to any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
  • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data
  • Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Christina Cho

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: ACTIVE
Contact: Leland L. Metheny
Phone: 216-844-0139

PRIMARY OBJECTIVES:

I. To define a post hematopoietic stem cell transplantation maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of inotuzumab ozogamicin in acute lymphocytic leukemia (ALL). (ALL Phase 1)

II. To assess the efficacy of inotuzumab ozogamicin as measured by disease free survival (DFS) at one year in ALL. (ALL Phase 2)

III. To define a post hematopoietic stem cell transplantation MTD and RP2D of inotuzumab ozogamicin in non-Hodgkin lymphoma (NHL). (NHL Phase 1)

IV. To assess the efficacy of inotuzumab ozogamicin as measured by DFS at one year in NHL. (NHL Phase 2)

SECONDARY OBJECTIVES:

I. To evaluate disease free survival (DFS), non-relapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year. (Phase 1 [for each cohort])

II. To determine the safety profile of inotuzumab ozogamicin after transplant including the incidence of myeloid toxicity and secondary graft failure and the rate of veno-occlusive disease / sinusoidal obstruction syndrome (VOD/SOS). (Phase 1 [for each cohort])

III. To determine if inotuzumab ozogamicin at these doses is effective at eradicating minimal residual disease (MRD) in this cohort of patients (ALL patients). (Phase 1 [for each cohort])

IV. To evaluate the pharmacokinetics of inotuzumab ozogamicin post autologous transplant (NHL patients). (Phase 1 [for each cohort])

V. To assess additional evidence of efficacy and safety as measured by NRM, relapse, relapse-related mortality and OS at 1 year. (Phase 2 [for each cohort])

VI. To determine if inotuzumab ozogamicin at these doses is effective at eradicating MRD in this cohort of patients (ALL patients). (Phase 2 [for each cohort])

VII. To confirm the safety profile of inotuzumab ozogamicin therapy after transplant including myeloid toxicity, secondary graft failure, and the rate of veno-occlusive disease / sinusoidal obstruction syndrome (VOD/SOS). (Phase 2 [for each cohort])

VIII. To evaluate the pharmacokinetics of inotuzumab ozogamicin post allogeneic and autologous transplant. (Phase 2 [for each cohort])

EXPLORATORY OBJECTIVES:

I. To describe the immunophenotype of patients receiving inotuzumab ozogamicin post allogeneic and autologous transplant.

II. To assess minimal residual disease post autologous transplant for NHL before, during, and after inotuzumab ozogamicin maintenance therapy.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day 1. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1-3 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Leland L. Metheny

  • Primary ID CASE1916
  • Secondary IDs NCI-2017-00826
  • Clinicaltrials.gov ID NCT03104491