NCT01925131

Brief Summary

This phase I trial studies the side effects and best dose of inotuzumab ozogamicin when given together with combination chemotherapy in treating patients with relapsed or refractory acute leukemia. Immunotoxins, such as inotuzumab ozogamicin, can find cancer cells that express cluster of differentiation (CD)22 and kill them without harming normal cells. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving inotuzumab ozogamicin together with combination chemotherapy may kill more cancer cells.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jun 2014

Longer than P75 for phase_1

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 15, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 19, 2013

Completed
10 months until next milestone

Study Start

First participant enrolled

June 13, 2014

Completed
7.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2022

Completed
3 months until next milestone

Results Posted

Study results publicly available

April 6, 2022

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2023

Completed
Last Updated

May 3, 2023

Status Verified

May 1, 2023

Enrollment Period

7.6 years

First QC Date

August 15, 2013

Results QC Date

March 8, 2022

Last Update Submit

May 1, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia

    To determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia \[B-ALL\], mixed phenotype, and Burkitt's). The MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicities is \< 33% using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

    28 days

Secondary Outcomes (2)

  • Response Rate (CR+CRi) Among Expansion Cohort

    Up to 3 years

  • Frequency and Severity of Toxicities

    Up to 3 years

Study Arms (6)

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 1

EXPERIMENTAL

Combination chemotherapy and inotuzumab ozogamicin - Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: cyclophosphamideDrug: vincristine sulfateDrug: prednisoneBiological: inotuzumab ozogamicinOther: laboratory biomarker analysis

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 2

EXPERIMENTAL

Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: cyclophosphamideDrug: vincristine sulfateDrug: prednisoneBiological: inotuzumab ozogamicinOther: laboratory biomarker analysis

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 3

EXPERIMENTAL

Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: cyclophosphamideDrug: vincristine sulfateDrug: prednisoneBiological: inotuzumab ozogamicinOther: laboratory biomarker analysis

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 4

EXPERIMENTAL

Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: cyclophosphamideDrug: vincristine sulfateDrug: prednisoneBiological: inotuzumab ozogamicinOther: laboratory biomarker analysis

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 5

EXPERIMENTAL

Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: cyclophosphamideDrug: vincristine sulfateDrug: prednisoneBiological: inotuzumab ozogamicinOther: laboratory biomarker analysis

Treatment (combination chemotherapy and inotuzumab ozogamicin) - MTD

EXPERIMENTAL

Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: cyclophosphamideDrug: vincristine sulfateDrug: prednisoneBiological: inotuzumab ozogamicinOther: laboratory biomarker analysis

Interventions

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 1Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 2Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 3Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 4Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 5Treatment (combination chemotherapy and inotuzumab ozogamicin) - MTD

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS
Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 1Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 2Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 3Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 4Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 5Treatment (combination chemotherapy and inotuzumab ozogamicin) - MTD

Given PO

Also known as: DeCortin, Deltra
Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 1Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 2Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 3Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 4Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 5Treatment (combination chemotherapy and inotuzumab ozogamicin) - MTD

Given IV

Also known as: CMC-544
Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 1Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 2Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 3Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 4Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 5Treatment (combination chemotherapy and inotuzumab ozogamicin) - MTD

Correlative studies

Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 1Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 2Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 3Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 4Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 5Treatment (combination chemotherapy and inotuzumab ozogamicin) - MTD

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have a diagnosis of relapsed or refractory CD22-positive acute leukemia including B-ALL, mixed phenotype leukemia (biphenotypic), or Burkitt's leukemia based on World Health Organization (WHO) classification; patients with bilineal leukemia are excluded
  • Patients must have evidence of acute leukemia in their peripheral blood or bone marrow; patients must have \>= 5% blasts in the peripheral blood or bone marrow within 14 days prior to registration; at least \>= 20% of those blasts must be CD22-positive (surface) based on local immunophenotyping and histopathology
  • Patients must be refractory or have relapsed following prior induction therapy; a standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine
  • For sites with the B1931022 pharmaceutical trial open, precursor B-cell ALL patients from that site may be eligible for S1312 providing they meet the following criteria:
  • Patient is in second salvage or more; OR
  • Patient was treated on the standard of care arm of B1931022 and failed therapy
  • Patients may have received prior allogeneic transplant or autologous transplant; however, patients with prior allogeneic bone marrow transplant will be eligible only if both of the following conditions are met:
  • The transplant must have been performed \>= 90 days prior to registration
  • The patient must not have \>= grade 2 acute graft versus host disease (GvHD) or either moderate or severe limited chronic GvHD within 14 days prior to registration
  • Patients known to have Philadelphia chromosome positive (Ph+) ALL must have either failed treatment or been intolerant to treatment with at least two second or third generation tyrosine kinase inhibitors
  • Patients must not have received prior treatment with inotuzumab ozogamicin; previous treatment with other anti-CD22 antibodies must have been completed at least 90 days prior to registration
  • Patients must have Zubrod performance status 0-2
  • Patients must not have received any chemotherapy, investigational agents, or undergone major surgery within 14 days prior to registration with the following exceptions:
  • Monoclonal antibodies must not have been received for 1 week prior to registration
  • Chimeric antigen receptor (CAR) T-cells must not have been received for 28 days prior to registration.
  • +30 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaBurkitt Lymphoma

Interventions

CyclophosphamideVincristinePrednisoneInotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsCalicheamicinsAminoglycosidesGlycosidesCarbohydratesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
SWOG Statistician
Organization
SWOG Statistics and Data Management Center

Study Officials

  • Anjali Advani

    SWOG Cancer Research Network

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 15, 2013

First Posted

August 19, 2013

Study Start

June 13, 2014

Primary Completion

January 1, 2022

Study Completion

January 1, 2023

Last Updated

May 3, 2023

Results First Posted

April 6, 2022

Record last verified: 2023-05

Locations