Inotuzumab Ozogamicin for Refractory B Acute Lymphoblastic Leukemia

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Refractory B Acute Lymphoblastic Leukemia+3 MoreInotuzumab Ozogamicin - Biological
Eligibility
1 - 21
All Sexes
What conditions do you have?
Select

Study Summary

This trial is testing inotuzumab ozogamicin to see if it can help patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment.

Eligible Conditions
  • Refractory B Acute Lymphoblastic Leukemia
  • B Lymphoblastic Lymphoma
  • Refractory B-Cell Lymphoblastic Lymphoma
  • B-Cell Acute Lymphoblastic Leukemia (ALL)

Treatment Effectiveness

Effectiveness Progress

1 of 3

Study Objectives

1 Primary · 11 Secondary · Reporting Duration: Up to 5 years

Year 5
Changes in peripheral blood absolute B cell numbers and maturation of developing B cell populations with inotuzumab ozogamicin therapy (Cohorts 1 and 2)
Intracellular signaling pathways in leukemic blasts treated with inotuzumab ozogamicin (Cohorts 1 and 2)
Baseline, post Cycle 1, and at time of relapse
Change in CD22 site density (Cohorts 1 and 2)
Changes in CD22 surface expression (Cohorts 1 and 2)
Baseline, post-Cycle 1, and at time of relapse
Leukemic blast CD22 splice variants (Cohorts 1 and 2)
Cycles 1 and 2
Immunogenicity (Cohort 1)
Day 28
Pharmacokinetic (PK) parameters, i.e., inotuzumab ozogamicin trough levels (Cohort 1)
Day 28
Incidence of dose-limiting toxicities at recommended phase II dose (RP2D) (Cohort 1)
Year 3
Event free survival (EFS) (Cohort 1)
Year 3
Overall survival (Cohort 1)
Overall survival (OS) (Cohort 1)
Year 1
Incidence of adverse events of sinusoidal obstruction syndrome (SOS) of liver (Cohort 1 and 2)
Month 12
Incidence of SOS in patients who receive prophylaxis with ursodeoxycholic acid (UDCA) during inotuzumab ozogamicin therapy (Cohorts 1 and 2)
Serum levels of candidate SOS biomarkers Ang2 and L ficolin (Cohorts 1 and 2)
Up to 2 cycles
Level of MRD by next-generation high-throughput sequencing (HTS) techniques (Cohorts 1 and 2)
Level of minimal residual disease (MRD) assessed in bone marrow by flow cytometry (Cohort 1 and 2)
Day 42
Morphologic response (CR/CRi) (Cohort 2)
Up to 28 days
Morphologic response (complete response [CR]+ incomplete hematologic recovery [CRi]) following one cycle of treatment with inotuzumab ozogamicin (Cohort 1)
Up to 3 years
Duration of CR, CRi (Cohort 1)
Up to 5 years
Interaction between CAR- T therapy and inotuzumab ozogamicin (Cohorts 1 and 2)
Up to 56 days
Morphologic response (CR + CRi) following 2 cycles of inotuzumab ozogamicin therapy (Cohort1)
Day 42
Incidence of dose-limiting toxicities at the selected dose level of inotuzumab ozogamicin in combination with the augmented modified Berlin-Frankfurt-Munster (mBFM) consolidation chemotherapy (Cohort 2)

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Side Effects for

Phase 1 - Dose-Finding: IV Inotuzumab Ozogamicin 1.6 mg/m^2
50%Fatigue
42%Constipation
42%Nausea
33%Vomiting
33%Thrombocytopenia
25%Aspartate aminotransferase increased
17%Neutropenia
17%Decreased appetite
17%Headache
8%Presyncope
8%Wheezing
8%Encephalopathy
8%Central nervous system neoplasm
8%Pain
8%Lymph node pain
8%Splenomegaly
8%Sinusitis
8%Odynophagia
8%Catheter site erythema
8%Insomnia
8%Disease progression
8%Septic shock
8%Pyrexia
8%Oropharyngeal pain
8%Rhinorrhoea
8%Pruritus
8%Rash
8%Hypoaesthesia
8%Weight decreased
8%Tremor
8%Dyspnoea exertional
8%Skin exfoliation
8%Hyperkeratosis
8%Influenza
8%Alanine aminotransferase increased
8%Bacteraemia
8%Blood creatinine increased
8%Anaemia
8%Conjunctival haemorrhage
8%Asthenia
8%Tonsillar hypertrophy
This histogram enumerates side effects from a completed 2016 Phase 2 trial (NCT01363297) in the Phase 1 - Dose-Finding: IV Inotuzumab Ozogamicin 1.6 mg/m^2 ARM group. Side effects include: Fatigue with 50%, Constipation with 42%, Nausea with 42%, Vomiting with 33%, Thrombocytopenia with 33%.

Trial Design

2 Treatment Groups

Cohort II (inotuzumab ozogamicin, mBFM chemotherapy)
1 of 2
Cohort I (inotuzumab ozogamicin)
1 of 2

Experimental Treatment

80 Total Participants · 2 Treatment Groups

Primary Treatment: Inotuzumab Ozogamicin · No Placebo Group · Phase 2

Cohort II (inotuzumab ozogamicin, mBFM chemotherapy)Experimental Group · 13 Interventions: Diagnostic Imaging, Biospecimen Collection, Vincristine, Pegaspargase, Bone Marrow Aspiration and Biopsy, Calaspargase Pegol-mknl, Cyclophosphamide, Lumbar Puncture, Methotrexate, Leucovorin Calcium, Cytarabine, Mercaptopurine, Inotuzumab Ozogamicin · Intervention Types: Procedure, Procedure, Drug, Drug, Procedure, Drug, Drug, Procedure, Drug, Drug, Drug, Drug, Biological
Cohort I (inotuzumab ozogamicin)
Biological
Experimental Group · 1 Intervention: Inotuzumab Ozogamicin · Intervention Types: Biological
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Biospecimen Collection
2004
Completed Phase 1
~670
Vincristine
FDA approved
Asparaginase Escherichia coli
FDA approved
Calaspargase Pegol-mknl
2008
Completed Phase 3
~170
Cyclophosphamide
FDA approved
Lumbar Puncture
2006
Completed Phase 2
~210
Methotrexate
FDA approved
Calcium
Not yet FDA approved
Cytarabine
FDA approved
Mercaptopurine
FDA approved
Inotuzumab ozogamicin
FDA approved

Trial Logistics

Trial Timeline

Screening: ~3 weeks
Treatment: Varies
Reporting: up to 5 years

Who is running the clinical trial?

Children's Oncology GroupLead Sponsor
448 Previous Clinical Trials
236,430 Total Patients Enrolled
1 Trials studying Refractory B Acute Lymphoblastic Leukemia
38 Patients Enrolled for Refractory B Acute Lymphoblastic Leukemia
National Cancer Institute (NCI)NIH
13,073 Previous Clinical Trials
41,138,828 Total Patients Enrolled
10 Trials studying Refractory B Acute Lymphoblastic Leukemia
610 Patients Enrolled for Refractory B Acute Lymphoblastic Leukemia
Maureen M O'BrienPrincipal InvestigatorChildren's Oncology Group

Eligibility Criteria

Age 1 - 21 · All Participants · 10 Total Inclusion Criteria

Mark “Yes” if the following statements are true for you:
Leukemic blasts must show evidence of CD22 on the surface when tested using flow cytometry with a bone marrow aspirate sample, preferably with PE as the fluorophore.
Your age must be between one and 22 years at the time of enrollment.
You have been diagnosed with either B-ALL or B lymphoblastic lymphoma (B-LL) and your bone marrow blast count is at least 5%
Individuals with a prior diagnosis of B-LL and an M2 or M3 marrow at the time of enrollment are eligible for this study.
Patients with ALL or B-LL displaying M2 morphology must have a local assessment demonstrating at least 5% blasts through flow cytometry, FISH testing or another molecular approach.
You have had more than one relapse.
You have a primary refractory disease with two or more prior induction attempts.
You have experienced a relapse that was not responsive to one or more re-induction attempts.
For Cohort 1, there must not have been a relapse after hematopoietic stem cell transplantation.
If a bone marrow aspirate sample is inadequate or not feasible due to patient's clinical status, flow cytometry of peripheral blood specimen may be substituted if the circulating blasts are 1,000/uL; alternatively, CD22 expression can be determined from an immunohistochemistry analysis of a bone marrow biopsy.