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

NCT03214666 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2015LS167HM2015-39
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

High-risk Myelodysplastic Syndromes; Acute Myelogenous Leukemia; Systemic Mastocytosis; Mast Cell Leukemia

Keywords

Myelodysplastic Syndromes (MDS); Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (2)

• 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.

  Day 1 (start of GTB-3550 therapy)

• 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.

  Day 28 relative to the start of GTB-3550 therapy

Secondary Outcomes (3)

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

  Day 28 relative to the start of GTB-3550 therapy

• Overall Survival (OS)

  6 Months

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

  After Day 28 Relative to GTB-3550 Therapy

Study Arms (2)

GTB-3550 TriKE® (Phase I: Dose Finding Component)

EXPERIMENTAL

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

GTB-3550 TriKE® Only (Phase II: Extended Component)

EXPERIMENTAL

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

Interventions

GTB-3550 TriKE® Phase I DRUG

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

Also known as: CD16/IL-15/CD33

GTB-3550 TriKE® (Phase I: Dose Finding Component)

GTB-3550 TriKE® Phase II DRUG

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

Also known as: CD16/IL-15/CD33

GTB-3550 TriKE® Only (Phase II: Extended Component)

Eligibility Criteria

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

You may qualify if:

• 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.
• At least 18 years of age

You may not qualify if:

• 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

Sponsors & Collaborators

• GT Biopharma, Inc.: lead

Study Sites (2)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Mastocytosis, Systemic; Leukemia, Mast-Cell; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Mast Cell Activation Disorders; Immune System Diseases; Bone Marrow Diseases

Limitations and Caveats

This trial was terminated due to plans to clinically advance a modified second generation TriKE, requiring a new phase 1 study. Given this early termination, the maximal tolerated dose was not reached and the study did not proceed to phase 2. As only 12 participants were enrolled, the outcomes are presented in summary/descriptive format only.

Results Point of Contact

• Title: Dr. Gregory Berk
• Organization: GT Biopharma, Inc.

gb@gtbiopharma.com

925-719-3531

Study Officials

• Mark B Juckett, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2017
• First Posted: July 11, 2017
• Study Start: January 1, 2020
• Primary Completion: August 2, 2021
• Study Completion: September 29, 2021
• Last Updated: November 10, 2022
• Results First Posted: November 10, 2022

Record last verified: 2022-10

Locations

US (2)