Clinical trial NCT01363297: Study Evaluating Inotuzumab Ozogamicin In Acute Lymphocytic Leukemia
Official title: An Open-label, Phase 1/2 Study Of Inotuzumab Ozogamicin In Subjects With Relapsed Or Refractory Cd22-positive Acute Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lymphocytic Leukemia
Keywords: Relapsed/Refractory Acute Lymphocytic Leukemia (ALL)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: UCB Pharma
First posted: 2011-06-01
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: The Phase 1 portion of this study will assess the safety, tolerability and efficacy at increasing dose levels of inotuzumab ozogamicin in subjects with CD22-positive relapsed or refractory adult acute lymphocytic leukemia (ALL) in order to select the recommended phase 2 dose (RP2D) and schedule. The Phase 2 portion of the study will evaluate the efficacy of inotuzumab ozogamicin as measured by hematologic remission rate (CR + CRi) in patients in second or later salvage status.


Eligibility criteria: Inclusion Criteria:

* Subjects with CD22-positive ALL with either refractory disease (i.e. disease progression or no response while receiving their most recent prior anti-cancer therapy), or relapsed disease (i.e. response to their most recent prior anti-cancer therapy with subsequent relapse). Subjects enrolled in the Phase 2 portion of the study must be due to receive salvage 2 or later therapy.
* Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor.
* Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

* Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia.
* Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy within 4 months, or active graft versus host disease (GvHD) at study entry.
* Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).

Primary outcomes:
measure: Percentage of Participants Reporting Dose Limiting Toxicities (DLTs) During the Phase 1 Dose-Finding Phase
timeFrame: Cycle 1
measure: Percentage of Participants With Preliminary Satisfactory Response (Complete Response [CR], CR With Incomplete Count Recovery [CRi], Partial Response [PR], or Resistant Disease [RD]) Indicating Disease Stability After First Dose During Phase 1 Dose-Finding
timeFrame: From screening to progressive disease or another induction therapy started, up to approximately 2 years
measure: Percentage of Participants With CR or CRi During Phase 2
timeFrame: From screening to progressive disease or another induction therapy started, up to approximately 2 years
measure: Percentage of Participants With CR, CRi or PR During the Phase 1 Expansion Phase
timeFrame: From screening to progressive disease or another induction therapy started, up to approximately 2 years
Secondary outcomes:
measure: Percentage of Participants With CR, CRi or PR in Phase 2
timeFrame: From screening to progressive disease or another induction therapy started, up to approximately 2 years
measure: Number of Participants With Minimal Residual Disease (MRD) Negativity in Participants Achieving CR and CRi
timeFrame: From screening to progressive disease or another induction therapy started, up to approximately 2 years
measure: Percentage of Participants With CR or CRi by Cytogenetic Category
timeFrame: From screening to progressive disease or another induction therapy started, up to approximately 2 years
measure: Percentage of Participants Who Had a Post-Treatment Stem-Cell Transplant (SCT)
timeFrame: Up to approximately 2 years from first dose
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years from first dose
measure: Duration of Remission (DoR1) for Participants Who Achieved CR or CRi
timeFrame: Up to approximately 2 years from first dose
measure: Duration of Response (DoR) for Participants Who Achieved CR/CRi or PR
timeFrame: Up to approximately 2 years from first dose
measure: Overall Survival (OS)
timeFrame: Up to approximately 2 years from first dose
measure: Time to Remission for Participants Who Achieved CR or CRi
timeFrame: Up to approximately 2 years from first dose
measure: Time to Response for Participants Who Achieved CR/CRi or PR
timeFrame: Up to approximately 2 years from first dose
measure: Time to MRD Negativity for Participants Who Achieved CR or CRi
timeFrame: Screening, Day 21 of Cycles 1 to 6 and up to 4 to 6 weeks after the last dose (up to 34 weeks)
measure: Duration of Follow-Up
timeFrame: From first dose up to approximately 2 years
measure: Percentage of Cluster of Differentiation-22 Positive (CD22+) Leukemic Blasts in Abnormal B Cells in Blood by Visit
timeFrame: Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
measure: Percentage of CD22+ Leukemic Blasts in Abnormal B Cells in Bone Marrow by Visit
timeFrame: Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4
measure: Messenger Ribonucleic Acid (mRNA) Gene Expression
timeFrame: Predose and postdose on Days 1 and 15 of Cycle 1
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford Unversity Cancer Clinical Trials Office
state: California
city: Palo Alto
country: United States
facility: Stanford Unversity Hospital and Clinics, CTRU
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Stanford
country: United States
facility: Stanford University Hospital and Clinics
state: California
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital (BWH)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute at Farmington Hills
state: Michigan
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
citation: Stock W, Martinelli G, Stelljes M, DeAngelo DJ, Gokbuget N, Advani AS, O'Brien S, Liedtke M, Merchant AA, Cassaday RD, Wang T, Zhang H, Vandendries E, Jabbour E, Marks DI, Kantarjian HM. Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia. Cancer. 2021 Mar 15;127(6):905-913. doi: 10.1002/cncr.33321. Epub 2020 Nov 24.
citation: DeAngelo DJ, Stock W, Stein AS, Shustov A, Liedtke M, Schiffer CA, Vandendries E, Liau K, Ananthakrishnan R, Boni J, Laird AD, Fostvedt L, Kantarjian HM, Advani AS. Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study. Blood Adv. 2017 Jun 27;1(15):1167-1180. doi: 10.1182/bloodadvances.2016001925. eCollection 2017 Jun 27.