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High-risk Myelodysplastic SyndromesPhase 1/2NCT03214666

GTB-3550 Tri-Specific Killer Engager (TriKE®) for High Risk Hematological Malignancies

A Phase 1/2 study testing GTB-3550 TriKE® Phase I and GTB-3550 TriKE® Phase II in people with High-risk Myelodysplastic Syndromes and Acute Myelogenous Leukemia, run by GT Biopharma, Inc. at 2 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 is a multi-center Phase I/II clinical trial of GTB-3550 (CD16/IL-15/CD33) tri-specific killer cell engager (TriKE®) for the treatment of CD33-expressing high risk myelodysplastic syndromes, refractory/relapsed acute myeloid leukemia or advanced systemic mastocytosis. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
GTB-3550 TriKE® Phase I and GTB-3550 TriKE® Phase II
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesUnited States
Study dates
1 Jan 2020to 29 Sep 2021
Phase
Phase 1/2
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

  • Diagnosis of one of the following CD33-expressing myeloid malignancies with greater than or equal to 50% CD33+ target cells with no good standard of care treatment options including:
  • High Risk Myelodysplastic Syndromes (MDS) progressive on two or more prior regimens and requiring treatment that meets at least one of the following:
  • Revised International Prognostic Scoring System (IPSS-R) High or Very High Risks
  • World Health Organization (WHO) Classification: Refractory anemia with excess blasts-1 (RAEB-1) or RAEB-2
  • Poor and very-poor risk cytogenetic abnormality as defined by the IPSS-R cytogenetic classifications
  • WHO Based Prognostic Scoring System (WPSS): High or Very High Risk
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  • Therapy related MDS and not a candidate for induction chemotherapy or had an inadequate treatment response after induction chemotherapy.
  • Refractory or Relapsed Acute Myelogenous Leukemia (AML) meeting at least one of the following:
  • Refractory AML defined as failure to achieve remission after at least 3 induction attempts
  • Elderly AML not fit for induction therapy can be enrolled after 2 failed inductions
  • Relapsed AML
  • Not a candidate for hematopoietic stem cell transplant (HSCT), at least one re-induction attempt required
  • Prior HSCT relapse beyond 3 months may be included only if off immunosuppression for a minimum of 4 weeks and do not have graft-versus-host disease (GVHD)
  • Advanced systemic mastocytosis (defined as mast cell leukemia, aggressive systemic mastocytosis, and systemic mastocytosis associated with hematologic neoplasm) may enroll without any prior treatment, given there is no standard established therapy.
  • Inclusion Criteria: Age, Performance Status, Organ Function, Contraception Use
  • At least 18 years of age
  • Karnofsky score ≥ 70%
  • Adequate organ function within 14 days (30 days for cardiac and pulmonary) of study enrollment defined as:
  • Renal: an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2
  • Hepatic: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and total bilirubin within normal range
  • Pulmonary function: Diffusing capacity for carbon monoxide (DLCO) corrected (ml/min/mm Hg) defined as no more than 5 units below lower limit of normal (Common Terminology Criteria for Adverse Events [CTCAE] v5 Grade 1 carbon monoxide diffusing capacity decreased) based on patient's height, weight, and gender as reported by the institutional pulmonary function lab.
  • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia; left ventricular ejection fraction ≥ 45% by echocardiogram, multigated acquisition (MUGA) scan or cardiac MRI.
  • Absolute lymphocyte count (ALC) ≥ 200 cells/mm³ OR absolute circulating CD56+/CD3- NK cell count >25 cells/μl within the 14 days prior to start of therapy
  • Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment
  • Participant provides voluntary written consent signed before performance of any study-related procedure not part of normal medical care

Who cannot join

  • New or progressive pulmonary infiltrates on screening chest x-ray or chest computerized tomography (CT) scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving with associated clinical improvement after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
  • Uncontrolled bacterial, fungal or viral infections, known history of HIV
  • Active Hepatitis B or Hepatitis C (virus detectable by polymerase chain reaction [PCR]) - chronic asymptomatic viral hepatitis is allowed
  • Other concurrent active cancer within the last year (excluding non-melanoma skin cancers)
  • Severely clinically obese patients, BMI >38
  • Currently taking any over-the-counter (OTC), vitamin, mineral, or dietary supplement within 14 days prior to study drug administration on Day 1 and during study conduct that may confound study safety goals (e.g., St. John's wort). Questions should be discussed with GT Biopharma.
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  • Pregnant or breast feeding. The effect of GTB-3550 TriKE on the fetus is unknown. Females of childbearing potential must have a blood test within 7 days prior to enrollment to rule out pregnancy - must be repeated if not within 7 days of treatment initiation
  • History of central nervous system (CNS) malignancy or symptoms of active CNS disease
  • A family history of long QT syndrome or with a corrected QT (QTc) interval > 480 msec at screening
  • Currently taking medications known to prolong QT/QTc interval as the potential risk of QT/QTc prolongation is unknown in humans.
  • A candidate for potentially curative therapy, including hematopoietic cell transplant
  • Unwilling to remain within a 90 minute drive of the study center through at least Day 29

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Wisconsin Clinical Science Center

    Madison, Wisconsin, 53792

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: GTB-3550 (CD16/IL-15/CD33)Tri-Specific Killer Engager (TriKE®) for the Treatment of High Risk Myelodysplastic Syndromes, Refractory/Relapsed Acute Myeloid Leukemia and Advanced Systemic Mastocytosis

This is a multi-center Phase I/II clinical trial of GTB-3550 (CD16/IL-15/CD33) tri-specific killer cell engager (TriKE®) for the treatment of CD33-expressing high risk myelodysplastic syndromes, refractory/relapsed acute myeloid leukemia or advanced systemic mastocytosis. The hypothesis is that GTB-3550 TriKE® will induce natural killer cell function by targeting malignant cells as well as CD33+ myeloid derived suppressor cells (MDSC) which contribute to tumor induced immunosuppression. Because CD16 is the most potent activating receptor on natural killer (NK) cells, this single agent may induce a targeted anti-CD33+ tumor response.

Being tested
GTB-3550 TriKE® Phase I, GTB-3550 TriKE® Phase II
Keywords
Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML)
Medical subject headings
Leukemia, Myeloid, Acute, Mastocytosis, Systemic, Leukemia, Mast-Cell, Myelodysplastic Syndromes

What participants receive

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

  • GTB-3550 TriKE® Phase IDrug

    Also called CD16/IL-15/CD33

    The 1st two patients will be assigned Dose Level 1. The study statistician will assign each new cohort of 2 patients to the most appropriate dose level based on updated toxicity probabilities.

    • Dose Level 1 - 5 μg/kg/day
    • Dose Level 2 - 10 μg/kg/day
    • Dose Level 3 - 25 μg/kg/day
    • Dose Level 4 - 50 μg/kg/day
    • Dose Level 5 - 100 μg/kg/day
    • Dose Level 6 - 150 μg/kg/day
    • Dose Level 7 - 200 μg/kg/day

  • GTB-3550 TriKE® Phase IIDrug

    Also called CD16/IL-15/CD33

    Patients will receive the maximum tolerated dose (MTD) established during Phase I with monitoring guidelines to stop the study early for excessive toxicity.

Study groups in NCT03214666
Study groupRoleWhat they receive
GTB-3550 TriKE® (Phase I: Dose Finding Component)ExperimentalPatients receive a single course of GTB-3550 TriKE® at their assigned dose as 3 weekly treatment blocks. Each block consists of four consecutive 24 hour continuous infusions (over approximately 96 hours) of GTB-3550 TriKE® followed by a 72 hour break after Block #1 and #2. All treatment is given as an inpatient. The assigned dose will be calculated on a weight obtained within 5 days prior to or on day of the 1st dose. The dose is not be recalculated for subsequent treatment blocks.
Receives: Drug: GTB-3550 TriKE® Phase I
GTB-3550 TriKE® Only (Phase II: Extended Component)ExperimentalThe treatment schedule is identical to the dose finding component. The extended component uses a Simon's MiniMax two-stage design for continued enrollment using the maximum tolerated dose (MTD) established during Phase I with monitoring guidelines to stop the study early for excessive toxicity.
Receives: Drug: GTB-3550 TriKE® Phase II

What is being measured

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

  1. GTB-3550 Dosing Summary

    The study was terminated prior to reaching the maximal tolerated dose. This outcome measure presents information regarding the number of participants receiving each dose of GTB-3550.

    Measured: Day 1 (start of GTB-3550 therapy)

  2. GTB-3550 Extent of Treatment (Summary)

    This outcome measure summarizes the number of GTB-3550 treatment blocks participants received during the first cycle of treatment.

    Measured: Day 28 relative to the start of GTB-3550 therapy

Secondary outcomes (3)

  1. Number of GTB-3550 TriKE® Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]

    The number of unexpected events in relation to GTB-3550 TriKE®. TEAEs were measured up to Day 28 relative to GTB-3550 therapy.

    Measured: Day 28 relative to the start of GTB-3550 therapy

  2. Overall Survival (OS)

    Number of patients surviving at 6 months post-treatment on this study.

    Measured: 6 Months

  3. Number of Participants Experiencing a Reduction in Blast Count Post-GTB-3550 Therapy

    Blast count was measured at the time of standard of care disease assessment after GTB-3550 therapy. Blast percent was assessed by morphology and/or flow cytometry.

    Measured: After Day 28 Relative to GTB-3550 Therapy

Timeline

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

  1. First posted11 Jul 2017
  2. Study start1 Jan 2020
  3. Primary completion2 Aug 2021
  4. Study completion29 Sep 2021

Why it stopped: Development of GTB-3550 halted due to development of the second generation camelid nanobody TriKE drug product, GTB-3650.

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03214666
Sponsor's protocol ID
2015LS167
Other IDs
HM2015-39
Status last verified
Oct 2022
First submitted
7 Jul 2017
Last updated
10 Nov 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GTB-3550 TriKE® Phase I and GTB-3550 TriKE® Phase II in people with High-risk Myelodysplastic Syndromes and Acute Myelogenous Leukemia, run by GT Biopharma, Inc. at 2 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 25 inclusion and 12 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 10 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 combined 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.

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 10 Nov 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?

GTB-3550 Dosing Summary (time frame: Day 1 (start of GTB-3550 therapy)). The study lists 2 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 NCT03214666.

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 10 Nov 2022.

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