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Trial record 10 of 168 for:    IL-15

CD16/IL-15/CD33 Tri-Specific Killer Engagers (TriKEs) for High Risk Heme Malignancies

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ClinicalTrials.gov Identifier: NCT03214666
Recruitment Status : Not yet recruiting
First Posted : July 11, 2017
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is a single center Phase I/II clinical trial of CD16/IL-15/CD33 (161533) 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 161533 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 NK cells, this single agent may induce a targeted anti-CD33+ tumor response.

Condition or disease Intervention/treatment Phase
High-risk Myelodysplastic Syndromes Acute Myelogenous Leukemia Systemic Mastocytosis Mast Cell Leukemia Drug: 161533 Trike Phase I Drug: 161533 Trike Phase II Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CD16/IL-15/CD33 (161533) Tri-Specific Killer Engagers (TriKEs) for the Treatment of High Risk Myelodysplastic Syndromes, Refractory/Relapsed Acute Myeloid Leukemia and Advanced Systemic Mastocytosis
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : February 1, 2024
Estimated Study Completion Date : August 1, 2025


Arm Intervention/treatment
Experimental: 161533 TriKE (Phase I: Dose Finding Component)
Patients receive a single course of 161533 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 161533 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: 161533 Trike Phase I

Bolus Test Dose: 20% of Daily Continuous Infusion Dose.

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 - 200 μg/kg/day
Other Name: CD16/IL-15/CD33

Experimental: 161533 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: 161533 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 Name: CD16/IL-15/CD33




Primary Outcome Measures :
  1. Phase I Maximum Tolerated Dose (MTD) of 161533 TriKE Finding [ Time Frame: Day 28 ]
    To identify the maximum tolerated dose (MTD) of 161533 TriKE defined as the dose level that most closely corresponds to a dose limiting toxicity rate (DLT) of 20%

  2. Phase II Incidence of complete and partial remission due to 161533 TriKE treatment [ Time Frame: Day 42 ]
    The incidence of clinical response by Day 42 after the start of the 1st infusion.


Secondary Outcome Measures :
  1. Incidence of 161533 TriKE Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Day 28 ]
    The incidence of unexpected events in relation to 161533 TriKE

  2. Overall Survival (OS) [ Time Frame: 6 Months ]
    Incidence of survival of patients treated on this study



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Eligible Diseases

  • Diagnosis of one of the following CD33-expressing myeloid malignancies 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 (R-IPSS) Category (refer to Appendix III): INT-2 or High Risk
    • R-IPSS High or Very High Risks
    • WHO Classification: RAEB-1 or RAEB-2
    • Poor and very-poor risk cytogenetic abnormality as defined by the R-IPSS cytogenetic classifications
    • WHO Based Prognostic Scoring System (WPSS): High or Very High Risk
  • Therapy related MDS and not a candidate for induction chemotherapy. Would be eligible if treated with induction chemotherapy and had an inadequate treatment response.
  • 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
    • Relapsed AML

      • Not a candidate for stem cell transplant (HSCT), at least one re-induction attempt required
      • Prior HSCT relapse beyond 12 months without active GVHD requiring
  • 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, but not older than 75 years of age
  • Karnofsky score ≥ 70% (Appendix II)
  • 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 using Modification of Diet in Renal Disease equation
    • Hepatic: AST, ALT, and alkaline phosphatase ≤ 3 x upper limit of normal and total bilirubin ≤ 1.5 х upper limit of normal range (ULN)
    • Pulmonary function: DLCOcor on PFTs ≥80% expected
    • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia; left ventricular ejection fraction ≥ 45% by echocardiogram, MUGA or cardiac MRI.
  • Absolute lymphocyte count (ALC) ≥ 200 cells/mm³ and 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

  • Bacterial, fungal or viral infection that has not cleared with appropriate treatment
  • Known HIV positivity
  • Active Hepatitis B or Hepatitis C (virus detectable by PCR) - chronic asymptomatic viral hepatitis is allowed
  • Pregnant or breast feeding. The effect of 161533 TriKE on the fetus is unknown. Females of childbearing potential must have a blood test or urine study 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 malignancy or symptoms of active CNS disease
  • A family history of long QT syndrome or with a 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 (refer to Appendix VI for a list of prohibited medications for eligibility)
  • A candidate for potentially curative therapy, including hematopoietic cell transplant
  • Unwilling to remain in the greater Twin Cities metropolitan area through at least Day 29

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03214666


Contacts
Contact: Timothy Krepski 612-273-2800 tkrepsk1@fairview.org

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Sarah Cooley, MD Masonic Cancer Center, University of Minnesota

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03214666     History of Changes
Other Study ID Numbers: 2015LS167
HM2015-39 ( Other Identifier: University of Minnesota Masonic Cancer Center )
First Posted: July 11, 2017    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Masonic Cancer Center, University of Minnesota:
MDS
AML

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Mastocytosis
Mastocytosis, Systemic
Leukemia, Mast-Cell
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases