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

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ClinicalTrials.gov Identifier: NCT03290664
Recruitment Status : Terminated (Slow accrual)
First Posted : September 25, 2017
Last Update Posted : September 17, 2018
Sponsor:
Collaborator:
Miltenyi Biotec, Inc.
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Biological: CD3-/CD19- Biological: CD3-/CD56+ Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The first twenty-four patients enrolled in the study will be randomized to CD3-/CD19- or CD3-/CD56+ in a parallel comparison of the two products. Twelve patients will be randomized to each product. The chosen product will then be given to an additional 17 patients based on success of the primary endpoint. If one of the products achieves the necessary number of complete remissions during stage 1 (6 or more out of 12) but the other product does not, that product will continue onto stage 2. If neither product achieves the necessary number of CRs, then this approach will be deemed unworthy of further study.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 18, 2017
Actual Primary Completion Date : March 26, 2018
Actual Study Completion Date : September 12, 2018


Arm Intervention/treatment
Experimental: CD3-/CD19- Infusion Biological: CD3-/CD19-
CD3-/CD19- will be infused along with IL-2 on Day 0 following a preparative regimen of Fludarabine and Cyclophosphamide.

Experimental: CD3-/CD56+ Infusion Biological: CD3-/CD56+
CD3-/CD56+ will be infused along with IL-2 on Day 0 following a preparative regimen of Fludarabine and Cyclophosphamide.




Primary Outcome Measures :
  1. Complete Remission [ Time Frame: Day 42 ]

    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 :
  1. NK Cell Expansion/Persistence [ Time Frame: Day 42 ]
    Defined as ≥ 100 donor derived NK cells per μl blood

  2. Treatment Related Adverse Events [ Time Frame: Day 42 ]
    Incidence of treatment related adverse events

  3. Infusional Toxicities [ Time Frame: Day 42 ]
    Incidence of infusional toxicities

  4. Treatment related mortality [ Time Frame: Day 100 ]
    Incidence of treatment related mortality

  5. Proceeding to hematopoietic cell transplantation [ Time Frame: 3 months ]
    Incidence subjects eligible to proceeding to hematopoietic cell transplantation. Eligibility is defined by having a remission status as defined in the primary outcome.

  6. aGvHD [ Time Frame: Day 42 ]
    Incidence of acute graft versus host disease (aGvHD)

  7. Overall survival at 12 months [ Time Frame: 12 months ]
    Incidence of overall survival

  8. Overall survival at 24 months [ Time Frame: 24 months ]
    Incidence of overall survival

  9. Disease free survival at 12 months [ Time Frame: 12 months ]
    Incidence of disease free survival

  10. Disease free survival at 24 months [ Time Frame: 24 months ]
    Incidence of disease free survival



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03290664


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

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03290664     History of Changes
Other Study ID Numbers: 2014LS005
MT2014-02 ( Other Identifier: Masonic Cancer Center )
First Posted: September 25, 2017    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms