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Acute Myeloid LeukemiaPhase 1NCT03922477

A Study Evaluating the Safety and Pharmacokinetics of Atezolizumab Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia

A Phase 1 study testing Atezolizumab and Hu5F9-G4 in people with Acute Myeloid Leukemia, run by Hoffmann-La Roche at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This Phase Ib study is designed to evaluate the safety and pharmacokinetics of atezolizumab when given in combination with Hu5F9-G4 to patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Atezolizumab and Hu5F9-G4
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
4 sitesUnited States
Study dates
8 Oct 2019to 3 Nov 2020
Phase
Phase 1
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

  • Life expectancy of at least 12 weeks
  • Eastern Cooperative Oncology Group Performance Status 0-2
  • Documented and confirmed R/R AML per WHO classification, except acute promyelocytic leukemia, and lack of response to all therapies of known benefit
  • Adequate end-organ function
  • Negative HIV test at screening
  • Negative hepatitis B surface antigen (HBsAg) test at screening
Show all 12Show fewer
  • Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA <500 IU/mL at screening
  • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
  • Willingness and ability to provide pretreatment bone marrow aspirate and biopsy and agreement to provide subsequent bone marrow aspirates and biopsies during study treatment
  • For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
  • For women who are not postmenopausal or surgically sterile: requirement for a negative serum pregnancy test result within 14 days prior to initiation of study treatment

Who cannot join

  • Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease, or requiring transplant-related immunosuppression
  • Prior solid organ transplant
  • Evidence of active central nervous system (CNS) involvement by leukemia
  • Pregnancy or lactation or intention to become pregnant during the study or within 5 months after the final dose of atezolizumab and/or Hu5F9-G4, whichever is longer
  • History of idiopathic pulmonary fibrosis, organizing pneumonitis, drug-induced pneumonitis, or idiopathic pneumonitis
  • History of autoimmune disease. Patients with a history of autoimmune-related hypothyroidism who are on a stable dose of thyroid replacement may be eligible for this study. Patients with controlled Type 1 diabetes mellitus who are on a stable insulin regimen may be eligible for this study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of the following conditions are met: (1) Rash must cover <10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition that require psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
  • Treatment with investigational therapy within 14 days prior to initiation of study drug
  • Any approved AML-related therapy within 14 days prior to enrollment. Granulocyte colony-stimulating factor to treat neutropenic fever and/or infection is permitted. Hydroxyurea may be used throughout the trial to control peripheral blood blast counts in response to the first dose of study treatment and during the first 4 weeks of study treatment.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Yale

    New Haven, Connecticut, 06511

  • Columbia University

    New York, New York, 10032-3725

  • UC Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: A Phase Ib, Open-Label Study Evaluating the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia

This Phase Ib study is designed to evaluate the safety and pharmacokinetics of atezolizumab when given in combination with Hu5F9-G4 to patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Being tested
Atezolizumab, Hu5F9-G4
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab will be administered to participants by IV infusion at a fixed dose starting on Day 22 of Cycle 1. In subsequent cycles (Cycles 2 and beyond), IV atezolizumab will be given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle.

  • Hu5F9-G4Drug

    Two priming doses of 1 mg/kg of Hu5F9-G4 will be administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance will be given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle. Dosing for de-escalation, if needed: Hu5F9-G4 will be given as two priming doses of 1 mg/kg IV on Days 1 and 4, followed by loading doses of 10 mg/kg IV on Day 8 and 15 mg/kg on Day 11. Starting on Day 15, maintenance treatment with Hu5F9-G4 will be given by IV infusion at a dose of 15 mg/kg once a week (QW).

Study groups in NCT03922477
Study groupRoleWhat they receive
Atezolizumab + Hu5F9-G4ExperimentalAn initial safety evaluation will be performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 is initially safe and tolerable in participants an additional cohort with R/R AML will be evaluated to further test the safety and anti-tumor activity. If dose-limiting toxicities (DLT) are observed in >=33% of participants in this initial cohort, a dose de-escalation cohort will be enrolled. If less than 33% of enrolled and dosed participants in any given cohort experience a DLT, an expansion cohort of 15 participants will be enrolled at the highest tolerated dose for this combination. If a dose de-escalation cohort is needed, an expansion cohort will be enrolled at the lower tolerated dose for this combination.
Receives: Drug: Atezolizumab; Drug: Hu5F9-G4

What is being measured

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

  1. Percentage of Participants With Adverse Events

    Percentage of participants with at least one adverse event.

    Measured: Up to approximately 13 months after first participant enrolled

  2. Complete Remission (CR)

    The CR rate is assessed as the percentage of participants who achieve a CR, complete remission with incomplete platelet recovery (CRp), complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh) (as defined by the IWG 2003 and ELN 2010 criteria) after up to six cycles of combination therapy.

    Measured: Up to approximately 3 months after first participant enrolled

  3. Duration of Response (DOR)

    DOR is defined as the time from the initial response (CR, CRp, CRi, CRh, or partial remission [PR]) to the time of disease progression or death, whichever occurs first

    Measured: Up to approximately 3 months after first particpant enrolled

Secondary outcomes (11)

  1. Serum Concentrations of Atezolizumab

    C=cycle (cycle=28 days) ; D=day; PTFI=prior to first infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=month

    Measured: C1 D22 PTFI of Hu5F9-G4 and atezolizumab, and 30 minutes after atezolizumab infusion; C2 D8 PTFI; C2 D22 PTFI; C3 D22 PTFI; C4 D22 PTFI; C8 D22 PTFI; C12 D22 PTFI; C16 D22 PTFI; TDV (up to C16 D21);120 days after final dose of atezolizumab (UTA 37M)

  2. Serum Concentrations of Hu5F9-G4

    C=cycle (cycle=28 days); D=Day; PTFI=prior to first infusion; H=hour; AEOI=after end of infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=months; E=every; T=thereafter

    Measured: C1D1 PTFI&1H AEOI; C1D8 PTFI,&1H AEOI; C1D11 PTFI,&1H AEOI; C1D22 1H AEOI; C2D1 PTFI,&1H AEOI; C2D8 PTFI; C3D1 PTFI,&1H AEOI; C5D1 PTFI; C7D1 PTFI, C9D1 PTFI; C11D1 PTFI; C13D1 PTFI; C15D1 PTFI; C17D1&D1 E 2C T PTFI(UTA 37M);TDV(up to C16D21)(UTA 37M)

  3. Objective Response Rate

    Objective response rate is defined as the percentage of participants with a partial remission (PR) or better (i.e., CR + CRp + CRi + CRh+ PR).

    Measured: Up to approximately 3 months after first participant enrolled

  4. Event-Free Survival

    Event-free survival is defined as the time from study entry to the date of induction treatment failure or relapse from CR, CRp, CRh, CRi, or death from any cause.

    Measured: Up to approximately 3 months after first participant enrolled

  5. Leukemia-Free Survival

    Leukemia-free survival is defined (only for participants achieving a CR, CRp, CRh, or CRi) as the time from the date of achievement of remission (CR, CRp, or CRi) until the date of relapse from CR, CRp, CRh, CRi, or death from any cause.

    Measured: Up to approximately 3 months after first participant enrolled

  6. Overall Survival

    Overall survival is defined as time from study entry to the date of death from any cause.

    Measured: Up to approximately 13 months after first participant enrolled

  7. Progression-Free Survival

    Progression-free survival (Investigator) is defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.

    Measured: Up to approximately 3 months after first participant enrolled

  8. Rate of Transfusion Independence

    Rate of transfusion independence is defined as the percentage of participants who achieve transfusion independence (i.e., achieving any continuous 56-day window without requiring platelet or RBC transfusions) at any time during study treatment.

    Measured: Up to approximately 3 months after first participant enrolled

  9. Duration of Transfusion Independence

    Duration of transfusion independence is defined as the number of consecutive days of transfusion independence, measured from 1 day after the last transfusion to disease progression or subsequent transfusion.

    Measured: Up to approximately 3 months after first participant enrolled

  10. Incidence of Anti-Drug Antibodies (ADAs) Against Atezolizumab During the Study Relative to the Prevalence of ADAs at Baseline

    Measured: Baseline up to approximately 37 months

  11. Incidence of ADAs Against Hu5F9-G4 During the Study Relative to the Prevalence of ADAs at Baseline

    Measured: Baseline up to approximately 37 months

Timeline

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

  1. First posted22 Apr 2019
  2. Study start8 Oct 2019
  3. Primary completion3 Nov 2020
  4. Study completion3 Nov 2020

Why it stopped: The Sponsor decided to discontinue the development of atezolizumab in combination with magrolimab in the AML indication.

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03922477
Sponsor's protocol ID
GO40828
Status last verified
Dec 2021
First submitted
11 Apr 2019
Last updated
21 Feb 2022
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab and Hu5F9-G4 in people with Acute Myeloid Leukemia, run by Hoffmann-La Roche at 4 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 12 inclusion and 8 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: stopped early, as of the sponsor's last update on 21 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 21 Feb 2022). 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 With Adverse Events (time frame: Up to approximately 13 months after first participant enrolled). The study lists 3 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 NCT03922477.

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 21 Feb 2022.

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