Study Evaluating Inotuzumab Ozogamicin In Acute Lymphocytic Leukemia

NCT01363297 | Completed Phase 2 Results

• 2 other identifiers: B19310103129K6-1106
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 15

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.

Conditions

Acute Lymphocytic Leukemia

Keywords

Relapsed/Refractory Acute Lymphocytic Leukemia (ALL)

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants Reporting Dose Limiting Toxicities (DLTs) During the Phase 1 Dose-Finding Phase

  DLT was any of the following in the first cycle \& attributable to inotuzumab ozogamicin: any greater than or equal to (≥) Grade 4 non-hematologic toxicity except nausea/vomiting (if manageable with supportive care), alopecia, \& toxicities secondary to neutropenia \& sepsis; prolonged myelosuppression (absolute neutrophil count \[ANC\] less than \[\<\] 500 per microliter \[/µL\] or platelet count \<25,000/µL in bone marrow with \<5 percent (%) blasts \& no evidence of leukemia more than 45 days beyond the most recent dose of test article); any Grade 3 non-hematologic toxicity (excluding toxicities such as alopecia or those secondary to neutropenia \& sepsis) not resolving to ≥ Grade 2 within 7 days of the most recent dose of test article or was clinically significant irrespective of duration; any ≥ Grade 3 elevation of alanine aminotransferase, aspartate aminotransferase or bilirubin lasting ≥7 days; any test article related toxicity resulting in permanent discontinuation of test article.

  Cycle 1

• 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

  CR was the disappearance of leukemia indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was as for CR except with ANC \<1000/µL and/or platelets \<100,000/µL. PR was an improved or no worsening of acute lymphocytic leukemia indicated by no peripheral blood blasts, and/or at least a 50% decrease in the marrow blast percentage, compared to pre-treatment value, and marrow blast percentage ≥5% and less than or equal to (≤)25% and/or C2 extramedullary disease status. RD occurred if a participant survived ≥7 days following completion of initial treatment course and had persistent leukemia in the most recent peripheral blood smear or bone marrow and/or persistent disease involvement at any extramedullary site after completion of therapy.

  From screening to progressive disease or another induction therapy started, up to approximately 2 years

• Percentage of Participants With CR or CRi During Phase 2

  CR was defined as a disappearance of leukemia as indicated by \<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC \<1000/µL and/or platelets \<100,000/µL.

  From screening to progressive disease or another induction therapy started, up to approximately 2 years

• Percentage of Participants With CR, CRi or PR During the Phase 1 Expansion Phase

  CR was defined as a disappearance of leukemia as indicated by \<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC ≥1000/µL and platelets ≥100,000/µL. C1 extramedullary disease status was required. CRi was defined as CR except with ANC \<1000/µL and/or platelets \<100,000/µL. PR was defined as an improved or no worsening of acute lymphocytic leukemia as indicated by no peripheral blood blasts, and either or both of the following: at least a 50% decrease in the marrow blast percentage, compared to the pre-treatment value, and marrow blast percentage ≥5% and ≤25% and/or C2 extramedullary disease status.

  From screening to progressive disease or another induction therapy started, up to approximately 2 years

Secondary Outcomes (15)

• Percentage of Participants With CR, CRi or PR in Phase 2

  From screening to progressive disease or another induction therapy started, up to approximately 2 years

• Number of Participants With Minimal Residual Disease (MRD) Negativity in Participants Achieving CR and CRi

  From screening to progressive disease or another induction therapy started, up to approximately 2 years

• Percentage of Participants With CR or CRi by Cytogenetic Category

  From screening to progressive disease or another induction therapy started, up to approximately 2 years

• Percentage of Participants Who Had a Post-Treatment Stem-Cell Transplant (SCT)

  Up to approximately 2 years from first dose

• Progression Free Survival (PFS)

  Up to approximately 2 years from first dose

Study Arms (1)

Inotuzumab Ozogamicin

EXPERIMENTAL

Drug: Inotuzumab Ozogamicin

Interventions

Inotuzumab Ozogamicin DRUG

Part 1: Administered intravenously as 2 - 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total dose per cycle 0.8 mg/m\^2 to 2.0 mg/m\^2. Part 2 Expansion and Part 3 Phase 2: Administered intravenously as 3 weekly doses over a 28-day cycle for a maximum of 6 cycles. Total initial dose per cycle 1.8 mg/m\^2.

Also known as: CMC-544

Inotuzumab Ozogamicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead
• UCB Pharma: collaborator

Study Sites (15)

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

Stanford Unversity Cancer Clinical Trials Office

Palo Alto, California, 94304, United States

Location

Stanford Unversity Hospital and Clinics, CTRU

Palo Alto, California, 94304, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Stanford University Hospital and Clinics

Stanford, California, 94305, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital (MGH)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital (BWH)

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Karmanos Cancer Institute at Farmington Hills

Farmington Hills, Michigan, 48334, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (3)

• 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.

  PMID: 35622074 DERIVED

• 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.

  PMID: 33231879 DERIVED

• 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.

  PMID: 29296758 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2011
• First Posted: June 1, 2011
• Study Start: August 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: January 1, 2016
• Last Updated: April 13, 2017
• Results First Posted: April 13, 2017

Record last verified: 2017-03

Locations

US (15)