Clinical Trials /

CD8 Depleted, Non-engrafting, HLA Mismatched Unrelated Infusion With MDS and Secondary AML

NCT04620681

Description:

The purpose of the study is to determine the safety of an investigational treatment for myelodysplastic syndrome (MDS) after the first therapy (such as azacitidine or decitabine) stops working or after progression of MDS to acute myeloid leukemia (AML).

Related Conditions:
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Secondary Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CD8 Depleted, Non-engrafting, HLA Mismatched Unrelated Infusion With MDS and Secondary AML
  • Official Title: CD8 Depleted, Non-Engrafting, HLA Mismatched Unrelated Donor Lymphocyte Infusion in Patients With MDA and Secondary AML

Clinical Trial IDs

  • ORG STUDY ID: MCC-20042
  • SECONDARY ID: G6095
  • NCT ID: NCT04620681

Conditions

  • Myelodysplastic Syndromes
  • Secondary Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytesPhase 1 Dose Level 1
Standard of Care ChemotherapyPhase 1 Dose Level 1

Purpose

The purpose of the study is to determine the safety of an investigational treatment for myelodysplastic syndrome (MDS) after the first therapy (such as azacitidine or decitabine) stops working or after progression of MDS to acute myeloid leukemia (AML).

Detailed Description

      The purpose of the study is to determine the safety of an investigational treatment for
      myelodysplastic syndrome (MDS) after the first therapy (such as azacitidine or decitabine)
      stops working or after progression of MDS to acute myeloid leukemia (AML).

      Patients with advanced MDS are treated with hypomethylating agents (HMAs) such as azacitidine
      or decitabine. These medications can be effective for a few months to a few years, but
      usually lose effect eventually. This study is attempting to design a therapy called
      "non-engrafting, CD8 depleted donor lymphocyte infusion" or "NE-DLI" as a treatment for these
      diseases.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose Level 1ExperimentalAll participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 1: 1X10^6 CD4 T Cells/kg
  • CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes
  • Standard of Care Chemotherapy
Phase 1 Dose Level 2ExperimentalAll participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 2: 1X10^7 CD4 T Cells/kg
  • CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes
  • Standard of Care Chemotherapy
Phase 1 Dose Level 3ExperimentalAll participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 3: 5 X10^7 CD4 T Cells/kg
  • CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes
  • Standard of Care Chemotherapy
Phase 2 -Treatment at Maximum Tolerated Dose (MTD)ExperimentalAll participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at MTD.
  • CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes
  • Standard of Care Chemotherapy

Eligibility Criteria

        Inclusion Criteria:

        Myelodysplastic Syndrome (MDS) having failed hypomethylating agent (HMA) therapy cohort:

          -  Age 18-79 years, inclusive

          -  Pathologically confirmed MDS or myelodysplastic/myeloproliferative overlap (MDS/MPN)

          -  IPSS-R score intermediate, high or very high

          -  Must have failed therapy with an HMA (defined as lack of response by International
             Working Group criteria (1) or intolerance of the drug)

        Secondary Acute Myeloid Leukemia (sAML):

          -  Pathologically confirmed AML according to World Health Organization (WHO) criteria

          -  Evidence of an antecedent hematologic disorder (AHD) prior to acute leukemia including
             a known prior diagnosis of MDS, MPN or MDS/MPN or data suggestive of an AHD such as
             cytopenias, fibrosis, macrocytic anemia, cellular or dysplasia at or prior to the time
             of diagnosis. If available, MDS-defining karyotypes (-7/del(7q), -5/del(5q), del(13q),
             del(11q), del(12p), t(12p), del(9q), idic(X)(q13), t(17p) (unbalanced translocations)
             or i(17q) (ie, loss of 17p), t(11;16)(q23;p13.3), t(3;21)(q26.2;q22.1),
             t(1;3)(p36.3;q21), t(2;11)(p21;q23), inv(3)(q21q26.2), t(6;9)(p23;q34)) or somatic
             mutations in multiple genes including p53, TET2, JAK2, CALR, MPL, ASXL1, RUNX1, SRSF2,
             SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 would also confirm eligibility.

          -  Age 60-79 years, inclusive

          -  May be previously untreated

        For both cohorts:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Deemed eligible to receive cytotoxic chemotherapy

          -  Creatinine clearance (CrCl)>50ml/min

          -  Total bilirubin <2 mg/dL (except for patients with Gilbert's disease), AST and ALT <
             3x ULN

          -  Left Ventricular Ejection Fraction ≥ 50%

          -  Willing and able to participate in study assessments

        Exclusion Criteria:

          -  Patients who have had systemic chemotherapy or radiotherapy within 4 weeks (6 weeks
             for nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier.
             Hydroxyurea during this period may be given as a bridging therapy to maintain disease
             stability while awaiting treatment. Intrathecal chemotherapy within this time frame is
             permitted. Intrathecal chemotherapy may be continued during protocol therapy in order
             to consolidate or maintain a central nervous system (CNS) remission, but not to treat
             active CNS disease

          -  Acute promyelocytic leukemia, or the presence of t(15;17)

          -  Patients receiving any other investigational agents

          -  Uncontrolled concurrent illness including, but not limited to, ongoing and
             uncontrolled infection, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements

          -  Pregnant women are excluded from this study because there is an unknown but potential
             risk for adverse events in the fetus. Breastfeeding should be discontinued if the
             mother is treated. These potential risks may also apply to other agents used in this
             study

          -  Patients who have any debilitating medical or psychiatric illness that would preclude
             their giving informed consent or their receiving optimal treatment and follow-up

          -  Patients with a poor functional status of ECOG 3-4, or otherwise deemed unfit to
             tolerate induction chemotherapy.

          -  Patients with blastic transformation of chronic myelogenous leukemia are ineligible

          -  Exposure to a humanized mouse chimeric antibody, as this could sensitize patients to
             components of the CD8 depletion column that may be present in small amounts in the
             cell product

          -  Prior allogenic hematopoietic cell transplant
      
Maximum Eligible Age:79 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI)
Time Frame:Up to 60 days per dose level
Safety Issue:
Description:Maximum Tolerated Dose will be determined by testing increasing doses of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI).

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:Up to 12 months
Safety Issue:
Description:Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.
Measure:Progression Free Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Progression Free Survival is defined as the time from enrollment to date of progression or death, or censor at last follow-up date.
Measure:Overall Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Overall Survival is defined as the time from study enrollment to death from any cause or censored at last follow up date
Measure:Hematologic Response
Time Frame:Up to 12 months
Safety Issue:
Description:Hematologic response will be determined using International Working Group 2006 criteria for MDS patients and the International Working Group 2003 criteria for AML

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • MDS
  • sAML

Last Updated

March 16, 2021