Clinical Trials /

CNDO-109-AANK for AML in First Complete Remission (CR1)

NCT01520558

Description:

This is a multi-center, open-label, non-controlled, non-randomized dose-escalating Phase 1 clinical study designed to examine the safety of infusing escalating doses of CNDO-109-Activated Allogeneic Natural Killer Cells-(from a first or second degree relative), after a preparatory chemotherapy regimen, in adult patients with acute myeloid leukemia (AML) who are in their first complete remission at the time of enrollment, are not candidates for stem cell transplant, and are considered to be at high risk for recurrence.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CNDO-109-AANK for AML in First Complete Remission (CR1)
  • Official Title: A Phase 1/2 Study of CNDO-109-Activated Allogeneic Natural Killer Cells in Patients With High Risk Acute Myeloid Leukemia in First Complete Remission (CR1)

Clinical Trial IDs

  • ORG STUDY ID: CNDO109-001
  • NCT ID: NCT01520558

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
CNDO-109-AANK CellsCNDO-109-Activated Allogeneic Natural Killer CellsCNDO-109-AANK Cells Dose 1

Purpose

This is a multi-center, open-label, non-controlled, non-randomized dose-escalating Phase 1 clinical study designed to examine the safety of infusing escalating doses of CNDO-109-Activated Allogeneic Natural Killer Cells-(from a first or second degree relative), after a preparatory chemotherapy regimen, in adult patients with acute myeloid leukemia (AML) who are in their first complete remission at the time of enrollment, are not candidates for stem cell transplant, and are considered to be at high risk for recurrence.

Trial Arms

NameTypeDescriptionInterventions
CNDO-109-AANK Cells Dose 1ExperimentalIn stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the lowest of these three doses (dose 1) is 3×10^5 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3.
    CNDO-109-AANK Cells Dose 2ExperimentalIn stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the middle dose of these three doses (dose 2) is 1×10^6 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3.
      CNDO-109-AANK Cells Dose 3ExperimentalIn stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the highest dose of these three doses (dose 3) is 3×10^6 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3.

        Eligibility Criteria

                Inclusion Criteria:
        
                  1. The patient has pathologically documented AML and is in CR1 at the time of the
                     screening visit
        
                  2. The patient achieved CR1 within 10 weeks of the screening visit; the patient may have
                     received post-remission consolidation therapy (except for transplant) prior to the
                     screening visit
        
                  3. A bone marrow aspiration performed within 21 days prior to the start of pre-infusion
                     preparative therapy confirms the patient is in CR1
        
                  4. The patient has either refused or is not considered an appropriate immediate candidate
                     for transplantation and is considered to be at high risk for recurrence by having at
                     least one of the following prognostic factors:
        
                       -  High risk cytogenetics (-5, -7, del(5q), abnormal 3q, 11q23 translocations,
                          complex cytogenetics) or if cytogenetics are normal the presence of a FLT3
                          mutation without a NPM1 mutation
        
                       -  Age > 60 years
        
                       -  Antecedent hematological disorder (AHD)
        
                       -  AML that is considered to be therapy-related
        
                       -  FAB subtype M0 (minimally differentiated acute myeloblastic leukemia), M6 (acute
                          erythroid leukemias, including erythroleukemia (M6a) and pure erythroid leukemia
                          (M6b)), or M7 (acute megakaryoblastic leukemia)
        
                  5. The patient is male or female, age 18 years or older
        
                  6. The patient has an ECOG performance status of 0, 1, or 2
        
                  7. The patient has an available NK cell donor who is a HLA haploidentical first-degree
                     (parent, child, or sibling) or second-degree (child of a sibling) relative; minimum
                     testing will be for HLA-A, HLA-B, and HLA-DR with donors matched for 3/6, 4/6 or 5/6
                     antigens
        
                  8. The patient has an absence of coexisting medical problems that would significantly
                     increase the risk of the chemotherapy procedure (e.g. poor left ventricular ejection
                     fraction [LVEF<40%])
        
                  9. The patient has recovered from reversible toxicity from prior therapy. Permanent and
                     stable side effects or changes are acceptable if ≤ Grade 1 (CTCAE, v4.03)
        
                 10. The patient has serum creatinine <2×ULN and not rising for at least 2-4 weeks before
                     chemotherapy. If elevated, the 24-hour creatinine clearance must be >50 mL/min
        
                 11. The patient has serum total bilirubin < 2 g/dL (unless the patient has a diagnosis of
                     Gilbert's disease), SGOT (ALT) <3.5×ULN, and SGPT (AST) <3.5×ULN
        
                 12. The patient has an absolute neutrophil count (ANC) ≥1000/µL, platelets ≥100,000/µL and
                     is not transfusion dependent for platelets and/or red cells
        
                 13. The patient has LVEF ≥40% by ECHO or MUGA scan and no clinically significant
                     abnormalities in 12-lead ECG
        
                 14. The patient has a PT (or INR) and PTT up to 1.25×ULN
        
                 15. The patient must not be dependent on supplemental oxygen
        
                 16. The patient is using an effective contraceptive (per the institutional standard), if
                     procreative potential exists
        
                 17. The patient must be willing and able to comply with all study protocol requirements.
                     The patient or a legally authorized representative must fully understand all elements
                     of the informed consent and have signed the informed consent according to
                     institutional and federal regulatory requirements
        
                 18. The patient has not received an investigational chemotherapy within the last 28 days
                     prior to the screening visit and has never received investigational immunotherapy. In
                     addition, the patient must not receive treatment for AML (including treatment with
                     IL-2 or IFNγ) in the interval of time between the screening visit and initiation of
                     pre-infusion preparative therapy
        
                Exclusion Criteria:
        
                  1. The patient had a previous bone marrow or stem cell transplant
        
                  2. The patient is seropositive for HIV 1, HIV 2, HBV, or HCV
        
                  3. The patient has a psychiatric, addictive, neurological or other disorder that
                     compromises the ability to give informed consent or comply with study requirements
        
                  4. The patient is pregnant (confirmed by urine or serum pregnancy test) or lactating
        
                  5. The patient has a recently diagnosed active malignancy requiring therapy
        
                  6. The patient has an uncontrolled infection, or is receiving anti-fungal treatment for
                     an ongoing infection
        
                  7. The patient has known hypersensitivity to bovine proteins
        
                  8. The patient has any condition that will place the patient at undue risk or discomfort
                     as a result of adherence to study procedures
        
                  9. The patient requires treatment with corticosteroids at a dose > 0.1 mg/kg/day or has a
                     known allergy to DSMO
              
        Maximum Eligible Age:N/A
        Minimum Eligible Age:18 Years
        Eligible Gender:All
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:Define MTD
        Time Frame:up to 30 days post dose
        Safety Issue:
        Description:The primary objective is to define the maximum tolerated dose (MTD), or the maximum tested dose where multiple dose-limiting toxicities (DLTs) are not observed, of CNDO-109-Activated Allogeneic Natural Killer Cells infused after preparative chemotherapy, administered to patients with acute myeloid leukemia (AML) who are in their first complete remission (CR1) at the time of enrollment and are considered to be at high risk for recurrence. The MTD outcome measure is presented as number of participants with DLTs.

        Secondary Outcome Measures

        Measure:Additional Safety Profile Beyond MTD
        Time Frame:up to 360 days post dose
        Safety Issue:
        Description:Characterize the safety profile of CNDO-109-Activated Allogeneic Natural Killer Cells infusion after preparative therapy by measurement of adverse events, safety labs, vital signs, bone marrow biopsy/aspiration and physical examination.
        Measure:Efficacy
        Time Frame:from the date of documented CR until the first documented progression date or until day 360 post dose whichever is sooner
        Safety Issue:
        Description:Determine relapse free survival (RFS) and overall survival (OS) following infusion with CNDO-109-Activated Allogeneic Natural Killer Cells.

        Details

        Phase:Phase 1/Phase 2
        Primary Purpose:Interventional
        Overall Status:Active, not recruiting
        Lead Sponsor:Coronado Biosciences, Inc.

        Trial Keywords

        • Acute Myeloid Leukemia
        • High Risk Relapse
        • Complete Remission
        • Allogeneic Natural Killer Cells

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