Clinical Trials /

Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia

NCT03104491

Description:

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects. The Phase II portion of this study is to see what side effects are seen with medication after transplant. Inotuzumab ozogamicin is a combination of an antibody and chemotherapy. This means that it targets the acute lymphocytic leukemia (ALL) cell and can deliver the chemotherapy to the ALL cell. Research shows that in some patients, it has caused their disease to go back into remission. Inotuzumab ozogamicin is considered experimental in this study.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Suspended

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia
  • Official Title: Inotuzumab Ozogamicin Post-Transplant for Acute Lymphocytic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: CASE1916
  • NCT ID: NCT03104491

Conditions

  • CD22-positive Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
Inotuzumab OzogamicinInotuzumab Ozogamicin

Purpose

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects.

The Phase II portion of this study is to see what side effects are seen with medication after transplant.

Inotuzumab ozogamicin is a combination of an antibody and chemotherapy. This means that it targets the ALL cell and can deliver the chemotherapy to the ALL cell. Research shows that in some patients, it has caused their disease to go back into remission.

Inotuzumab ozogamicin is considered experimental in this study.

Detailed Description

Primary Objective Phase I: To define a post hematopoietic stem cell transplantation maximum tolerated dose of inotuzumab ozogamicin Phase II: To define the safety profile of inotuzumab ozogamicine therapy after allogeneic transplant.

Phase II: To determine the rate of veno-occlusive disease / sinusoidal obstruction syndrome (VOD/SOS).

Secondary Objective(s)

1. To evaluate non-relapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year.

2. To determine the incidence of myeloid toxicity and secondary graft failure.

3. To determine if inotuzumab at these doses are effective at eradicating MRD in this cohort of patients.

Study Design This is a Phase I/II study of inotuzumab ozogamicin for the treatment of patients who underwent allogeneic transplantation for ALL and have a high risk of relapse. The Phase I portion of this study will be a 3/3 dose escalation trial with cohort expansion at the maximum tolerated dose (MTD). Subjects will receive study treatment until relapse of disease, unacceptable toxicity, 30 days after cycle 4, or death, whichever occurs first.

Phase I: Inotuzumab Ozogamicin Dosing Escalation Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach.

Phase II: Inotuzumab Ozogamicin Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach. In order to be included in the safety profile endpoint review, subjects must have received at least of 1 cycle of treatment.

Trial Arms

NameTypeDescriptionInterventions
Inotuzumab OzogamicinExperimentalSubjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach.
  • Inotuzumab Ozogamicin

Eligibility Criteria

Phase I

Inclusion Criteria:

- Diagnosis of CD22-positive Acute Lymphoblastic Leukemia

- Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia

- Patients who are between T+40 and T+100 after allogeneic transplantation

- 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

- Patients who have evidence of donor chimerism after allogeneic transplantation.

- Philadelphia chromosome positive ALL must have failed at least 1 TKI

- ECOG Performance status ≤ 2

- Subjects must have the ability to understand and the willingness to sign a written informed consent document.

- Subjects must have ANC > 1,000 for 3 days and platelet transfusion independence as defined as a platelet count > 20,000 for 7 days.

Phase II

Inclusion Criteria:

- Diagnosis of CD22-positive Acute Lymphoblastic Leukemia

- Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia

- Patients who are between T+40 and T+100 after allogeneic transplantation

- 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

- Patients who have evidence of donor chimerism after allogeneic transplantation.

- Philadelphia chromosome positive ALL must have failed at least 1 TKI

- ECOG Performance status ≤ 2

- Subjects must have the ability to understand and the willingness to sign a written informed consent document.

- Subjects must have ANC > 1,000 for 3 days and platelet transfusion independence as defined as a platelet count > 20,000 for 7 days

Phase I/II

Exclusion Criteria:

- Patients with inadequate Organ Function as defined by:

- Creatinine clearance < 30ml/min

- Bilirubin ≥ 2X institutional upper limit of normal

- AST (SGOT) ≥ 2X institutional upper limit of normal

- ALT (SGPT) ≥ 2X institutional upper limit of normal

- GVHD grade III or IV.

- Active acute or chronic GVHD of the liver

- History of 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

- 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

Maximum Eligible Age:75 Years
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:Up to 112 days (16 weeks)
Safety Issue:
Description:Phase I Primary Outcome

Secondary Outcome Measures

Measure:Response Rate
Time Frame:Up to 1 year after initial treatment
Safety Issue:
Description:defined as the proportion of patients with a best overall response of eradicating MRD in this cohort of patients at the time each patient discontinues treatment with Inotuzumab Ozogamicin
Measure:Recurrence-free survival
Time Frame:Up to 1 year after initial treatment
Safety Issue:
Description:Time from initial treatment to progression, death, or one year, whichever comes first
Measure:Overall Survival
Time Frame:Up to 1 year after initial treatment
Safety Issue:
Description:Time from initial treatment to death or one year, whichever comes first
Measure:Incidence of myeloid toxicity
Time Frame:Up to 1 year after initial treatment
Safety Issue:
Description:Number of patients who develop myeloid toxicity while on study
Measure:Incidence of secondary graft failure
Time Frame:Up to 1 year after initial treatment
Safety Issue:
Description:Number of patients who develop secondary graft failure while on study

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Leland Metheny

Trial Keywords

  • allogeneic hematopoietic stem cell transplantation
  • donor chimerism

Last Updated

April 3, 2017