Clinical Trials /

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

NCT03214666

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Hematopoietic and Lymphoid Malignancy
  • Mast Cell Leukemia
  • Myelodysplastic Syndromes
  • Systemic Mastocytosis
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2015LS167
  • SECONDARY ID: HM2015-39
  • NCT ID: NCT03214666

Conditions

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

Interventions

DrugSynonymsArms
161533 Trike Phase ICD16/IL-15/CD33161533 TriKE (Phase I: Dose Finding Component)
161533 Trike Phase IICD16/IL-15/CD33161533 TriKE Only (Phase II: Extended Component)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
161533 TriKE (Phase I: Dose Finding Component)ExperimentalPatients 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.
  • 161533 Trike Phase I
161533 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.
  • 161533 Trike Phase II

Eligibility 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
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I Maximum Tolerated Dose (MTD) of 161533 TriKE Finding
Time Frame:Day 28
Safety Issue:
Description: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%

Secondary Outcome Measures

Measure:Incidence of 161533 TriKE Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:Day 28
Safety Issue:
Description:The incidence of unexpected events in relation to 161533 TriKE
Measure:Overall Survival (OS)
Time Frame:6 Months
Safety Issue:
Description:Incidence of survival of patients treated on this study

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • MDS
  • AML

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