Clinical Trials /

CD3-/CD19- vs CD3-/CD56+ Haplo NK for AML Pts Who Failed 1-2 Inductions

NCT03290664

Description:

This is a phase II trial of related donor HLA-haploidentical NK-cell based therapy for the treatment of newly diagnosed acute myelogenous leukemia (AML) (except acute promyelocytic leukemia) in persons who failed to achieve a complete remission (CR) after one or two standard induction attempts. Failure is defined as ≥ 30% bone marrow blasts in a bone marrow of at least 20% cellularity at the mid-cycle (~day 14) bone marrow biopsy or residual AML on ~day 28 bone marrow biopsy by morphology, flow, PCR or FISH.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CD3-/CD19- vs CD3-/CD56+ Haplo NK for AML Pts Who Failed 1-2 Inductions
  • Official Title: A Randomized Trial Comparing CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for Adults With Acute Myelogenous Leukemia Who Have Failed 1 or 2 Induction Attempts

Clinical Trial IDs

  • ORG STUDY ID: 2014LS005
  • SECONDARY ID: MT2014-02
  • NCT ID: NCT03290664

Conditions

  • Acute Myelogenous Leukemia

Interventions

DrugSynonymsArms
CD3-/CD19-CD3-/CD19- Infusion
CD3-/CD56+CD3-/CD56+ Infusion

Purpose

This is a phase II trial of related donor HLA-haploidentical NK-cell based therapy for the treatment of newly diagnosed acute myelogenous leukemia (AML) (except acute promyelocytic leukemia) in persons who failed to achieve a complete remission (CR) after one or two standard induction attempts. Failure is defined as ≥ 30% bone marrow blasts in a bone marrow of at least 20% cellularity at the mid-cycle (~day 14) bone marrow biopsy or residual AML on ~day 28 bone marrow biopsy by morphology, flow, PCR or FISH.

Trial Arms

NameTypeDescriptionInterventions
CD3-/CD19- InfusionExperimental
  • CD3-/CD19-
CD3-/CD56+ InfusionExperimental
  • CD3-/CD56+

Eligibility Criteria

        Inclusion Criteria:

          -  Newly diagnosed with acute myelogenous leukemia (except acute promyelocytic leukemia)
             and has failed one or two prior standard induction attempts. Failure is defined as:

               -  ≥ 30% bone marrow blasts in a bone marrow with at least 20% cellularity at
                  mid-cycle bone marrow biopsy or

               -  residual AML on ~ day 28 bone marrow biopsy by morphology, flow, PCR or FISH

          -  AML that progressed out of myelodysplastic syndrome (MDS) is eligible if the patient
             did not receive treatment directed at the MDS.

          -  Patients enrolling after only 1 failed induction attempt must meet at least one of the
             following additional eligibility criteria of high risk:

               -  ≥ 60 years of age

               -  adverse cytogenetics or molecular characteristics

                    -  (inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1

                    -  t(6;9)(p23;q34); DEK-NUP214

                    -  t(v;11)(v;q23); MLL rearranged

                    -  -5 or del(5q); -7; abnl(17p); complex karyotype

          -  Persons receiving a "non-standard" induction (i.e. one containing investigational
             agent(s)) will be considered for eligibility by Miltenyi on a case by case basis.

          -  Use of hydroxyurea is permitted to control blasts until the day chemotherapy is
             started.

          -  A history of AML related CNS involvement is allowed if most recent CSF analysis is
             negative at least 2 weeks prior to study treatment.

          -  ≥ 18 and <75 years of age

          -  Karnofsky performance status ≥ 60% (appendix IV)

          -  HLA-haploidentical related donor (aged 12 to 70 years) with donor/recipient match
             based on a minimum of intermediate resolution DNA based Class I typing of the A,B and
             C locus - refer to section 5 for donor selection.

          -  Adequate organ function within 14 days of study registration (30 days for pulmonary
             and cardiac) defined as:

               -  Creatinine: ≤ 2.0 mg/dL

               -  Hepatic: SGOT and SGPT < 5 x upper limit of institutional normal (ULN)

               -  Pulmonary: oxygen saturation ≥ 90% on room air

               -  Cardiac: LVEF ≥ 40% by echocardiogram, MUGA or cardiac MRI, no uncontrolled
                  angina, uncontrolled atrial or ventricular arrhythmias, or evidence of acute
                  ischemia or active conduction system abnormalities (rate controlled a-fib is not
                  an exclusion)

          -  Ability to be off prednisone and other immunosuppressive drugs for at least 3 days
             prior to the NK cell infusion (excluding preparative regimen pre-meds)

          -  Sexually active females of childbearing potential and males with partners of child
             bearing potential must agree to use appropriate birth control precautions during the
             study and for 3 months after the NK cell infusion

          -  Voluntary written consent prior to the performance of any research related procedures

        Exclusion Criteria:

          -  Pregnant or lactating as the treatments used in this study includes drugs that are FDA
             Pregnancy Category D - Positive evidence of human fetal risk based on adverse reaction
             data from investigational or marketing experience or studies in humans. Women of child
             bearing potential must have a negative pregnancy test within 14 days of study
             registration.

          -  Acute leukemias of ambiguous lineage

          -  AML that transformed from previously treated myelodysplastic syndromes

          -  Untreated CNS leukemia

          -  Prior hematopoietic transplant

          -  New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan
             that has not been cleared 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 including HIV - chronic
             asymptomatic viral hepatitis is allowed

          -  Known hypersensitivity to one or more of the study agents
      
Maximum Eligible Age:74 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Remission
Time Frame:Day 42
Safety Issue:
Description:Incidence of complete remission which is defined as the following disease statuses: absolute neutrophil count > 1,000/mm3, platelet count > 100,000/ mm3, no leukemic blast in the peripheral blood and < 5% blast in the marrow (CR), a morphologic complete remission with incomplete blood count recovery (CRi) leukemia clearance (< 5% marrow blast and no circulating peripheral blasts) and neutrophil recovery but with incomplete platelet recovery (CRp)

Secondary Outcome Measures

Measure:NK Cell Expansion/Persistence
Time Frame:Day 42
Safety Issue:
Description:Defined as ≥ 100 donor derived NK cells per μl blood
Measure:Treatment Related Adverse Events
Time Frame:Day 42
Safety Issue:
Description:Incidence of treatment related adverse events
Measure:Infusional Toxicities
Time Frame:Day 42
Safety Issue:
Description:Incidence of infusional toxicities
Measure:Treatment related mortality
Time Frame:Day 100
Safety Issue:
Description:Incidence of treatment related mortality
Measure:Proceeding to hematopoietic cell transplantation
Time Frame:3 months
Safety Issue:
Description:Incidence subjects eligible to proceeding to hematopoietic cell transplantation. Eligibility is defined by having a remission status as defined in the primary outcome.
Measure:aGvHD
Time Frame:Day 42
Safety Issue:
Description:Incidence of acute graft versus host disease (aGvHD)
Measure:Overall survival at 12 months
Time Frame:12 months
Safety Issue:
Description:Incidence of overall survival
Measure:Overall survival at 24 months
Time Frame:24 months
Safety Issue:
Description:Incidence of overall survival
Measure:Disease free survival at 12 months
Time Frame:12 months
Safety Issue:
Description:Incidence of disease free survival
Measure:Disease free survival at 24 months
Time Frame:24 months
Safety Issue:
Description:Incidence of disease free survival

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • AML

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