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Acute Lymphocytic LeukemiaPhase 2NCT01363297

Study Evaluating Inotuzumab Ozogamicin In Acute Lymphocytic Leukemia

A Phase 2 study testing Inotuzumab Ozogamicin in people with Acute Lymphocytic Leukemia, run by Pfizer at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Lymphocytic Leukemia
What is being tested?
Inotuzumab Ozogamicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
15 sitesUnited States
Study dates
Aug 2011to Jan 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Massachusetts General Hospital (MGH)

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital (BWH)

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope National Medical Center

    Duarte, California, 91010-3000

  • Karmanos Cancer Institute at Farmington Hills

    Farmington Hills, Michigan, 48334

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Stanford Unversity Cancer Clinical Trials Office

    Palo Alto, California, 94304

  • Stanford Unversity Hospital and Clinics, CTRU

    Palo Alto, California, 94304

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Stanford Cancer Institute

    Stanford, California, 94305

  • Stanford University Hospital and Clinics

    Stanford, California, 94305

Other trials in United States

About this study

Official title: An Open-label, Phase 1/2 Study Of Inotuzumab Ozogamicin In Subjects With Relapsed Or Refractory Cd22-positive Acute Lymphocytic Leukemia

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.

Being tested
Inotuzumab Ozogamicin
Keywords
Relapsed/Refractory Acute Lymphocytic Leukemia (ALL)
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Inotuzumab OzogamicinDrug

    Also called CMC-544

    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.

Study groups in NCT01363297
Study groupRoleWhat they receive
Inotuzumab OzogamicinExperimentalNot described
Receives: Drug: Inotuzumab Ozogamicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cycle 1

  2. 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.

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

  3. 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.

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

  4. 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.

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

Secondary outcomes (15)

  1. Percentage of Participants With CR, CRi or PR in 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. 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.

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

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

    MRD negativity was defined as <0.01% mononuclear cells.

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

  3. Percentage of Participants With CR or CRi by Cytogenetic Category

    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.

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

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

    Post-treatment SCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin.

    Measured: Up to approximately 2 years from first dose

  5. Progression Free Survival (PFS)

    PFS was defined as the time from Cycle 1 Day 1 to first documentation of PFS event (earliest date of objective progression [PD], treatment discontinuation due to global deterioration of health status, subsequent induction or transplant after best response of PR or resistant disease, relapse after CR or CRi, or death due to any cause). Participants last known to be 1) alive and 2) without a PFS event, were censored at the date of the last disease assessment that verified lack of event.

    Measured: Up to approximately 2 years from first dose

  6. Duration of Remission (DoR1) for Participants Who Achieved CR or CRi

    DoR1 was defined for participants who responded as the time from the date of first documentation of Complete Hematologic Response (CR or CRi) to the date of the first documentation of relapse after CR or CRi, treatment discontinuation due to global deterioration of health status) or to death due to any cause. Participants last known to be 1) alive and 2) without a DoR1 event, were censored at the date of the last disease assessment that verified lack of event.

    Measured: Up to approximately 2 years from first dose

  7. Duration of Response (DoR) for Participants Who Achieved CR/CRi or PR

    DoR was defined for participants who respond as the time from the date of first documentation of Hematologic Response (CR, CRi, or PR) to the date of the first documentation of DoR event (earliest date of PD, treatment discontinuation due to global deterioration of health status, first induction therapy or transplant after PR, relapse after CR or CRi or death due to any cause). Participants last known to be 1) alive and 2) without a DoR event, were censored at the date of the last disease assessment that verified lack of event.

    Measured: Up to approximately 2 years from first dose

  8. Overall Survival (OS)

    OS was defined as the time from Cycle 1 Day 1 to date of death due to any cause. If death was not documented, censoring occurred at the date at which the participant was last known to be alive.

    Measured: Up to approximately 2 years from first dose

  9. Time to Remission for Participants Who Achieved CR or CRi

    Time to remission was defined as the time from the date of first dose of study drug to the date of first documentation of hematologic remission (CR or CRi) in participants achieving remission during study therapy.

    Measured: Up to approximately 2 years from first dose

  10. Time to Response for Participants Who Achieved CR/CRi or PR

    Time to response was defined as the time from the date of first dose of study drug to the date of first documentation of hematologic response (CR, CRi, or PR).

    Measured: Up to approximately 2 years from first dose

  11. Time to MRD Negativity for Participants Who Achieved CR or CRi

    Time to MRD negativity was defined as the time from the date of first dose of study drug to the date of first documentation of MRD negativity.

    Measured: Screening, Day 21 of Cycles 1 to 6 and up to 4 to 6 weeks after the last dose (up to 34 weeks)

  12. Duration of Follow-Up

    Duration of follow-up was defined as the time from the date of first dose of study drug to the date of last contact for participants known to be alive.

    Measured: From first dose up to approximately 2 years

  13. Percentage of Cluster of Differentiation-22 Positive (CD22+) Leukemic Blasts in Abnormal B Cells in Blood by Visit

    CD22+ leukemic blasts assessed in abnormal B cells from blood (data from central laboratories only).

    Measured: Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4

  14. Percentage of CD22+ Leukemic Blasts in Abnormal B Cells in Bone Marrow by Visit

    CD22+ leukemic blasts assessed in abnormal B cells from bone marrow (data from central laboratories only).

    Measured: Pre-dose on Days 1 and 15 of Cycles 1 and 2, and Day 1 of Cycle 4

  15. Messenger Ribonucleic Acid (mRNA) Gene Expression

    Optional blood samples for pharmacogenomic parameters were collected during Cycle 1 prior to the start of the inotuzumab ozogamicin infusion (0 hours) and 1 hour post-dose (original Final Protocol and Protocol Amendments 1 and 2) or 3 hours post-dose (Protocol Amendments 3 and 4) on Day 1 and Day 15 from those participants who provided consent. Gene expression analysis of samples collected pre- and post-dosing was performed using 96-gene TaqMan® low density array cards to examine the concordance between clinical outcome and expression of genes such as those involved in DNA damage response, apoptosis, B-cell antigen expression, glutathione metabolism, drug transport and the phosphoinositide 3-kinase/mammalian target of rapamycin pathway. Expression for each gene was reported as a normalized value, 2^-change in (∆) threshold cycle (Ct), where ∆Ct is Ct^target gene minus Ct^reference genes, averaged.

    Measured: Predose and postdose on Days 1 and 15 of Cycle 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2011 (estimated)
  2. Study startAug 2011
  3. Primary completionAug 2014
  4. Study completionJan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01363297
Sponsor's protocol ID
B1931010
Other IDs
3129K6-1106
Status last verified
Mar 2017
First submitted
11 May 2011
Last updated
13 Apr 2017
Data monitoring committee
No

Publications

  • 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.

    PubMed 35622074

  • 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.

    PubMed 33231879

  • 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.

    PubMed 29296758

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Inotuzumab Ozogamicin in people with Acute Lymphocytic Leukemia, run by Pfizer at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Reporting Dose Limiting Toxicities (DLTs) During the Phase 1 Dose-Finding Phase (time frame: Cycle 1). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01363297, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2017.

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