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

October 14, 2022 updated by: GT Biopharma, Inc.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center, University of Minnesota
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Clinical Science Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: Eligible Diseases

  • 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
  • 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

Exclusion Criteria

  • 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.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: GTB-3550 TriKE® (Phase I: Dose Finding Component)
Patients 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.
Drug: GTB-3550 TriKE® Phase I

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
Other Names:
  • CD16/IL-15/CD33
Experimental: GTB-3550 TriKE® Only (Phase II: Extended Component)
The 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.
Drug: GTB-3550 TriKE® Phase II
Patients will receive the maximum tolerated dose (MTD) established during Phase I with monitoring guidelines to stop the study early for excessive toxicity.
Other Names:
  • CD16/IL-15/CD33

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
GTB-3550 Dosing Summary
Time Frame: Day 1 (start of GTB-3550 therapy)
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.
Day 1 (start of GTB-3550 therapy)
GTB-3550 Extent of Treatment (Summary)
Time Frame: Day 28 relative to the start of GTB-3550 therapy
This outcome measure summarizes the number of GTB-3550 treatment blocks participants received during the first cycle of treatment.
Day 28 relative to the start of GTB-3550 therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of GTB-3550 TriKE® Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
Time Frame: Day 28 relative to the start of GTB-3550 therapy
The number of unexpected events in relation to GTB-3550 TriKE®. TEAEs were measured up to Day 28 relative to GTB-3550 therapy.
Day 28 relative to the start of GTB-3550 therapy
Overall Survival (OS)
Time Frame: 6 Months
Number of patients surviving at 6 months post-treatment on this study.
6 Months
Number of Participants Experiencing a Reduction in Blast Count Post-GTB-3550 Therapy
Time Frame: After Day 28 Relative to 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.
After Day 28 Relative to GTB-3550 Therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GT Biopharma, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mark B Juckett, MD, Masonic Cancer Center, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 2, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 29, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 7, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 11, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 10, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2015LS167
  • HM2015-39 (Other Identifier: University of Minnesota Masonic Cancer Center)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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