Haploidentical Natural Killer (NK) Cells With Epratuzumab for Relapsed Acute Lymphoblastic Leukemia (ALL)
Condition: Leukemia; Pediatric Cancer
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Epratuzumab; Fludarabine; Cyclophosphamide; Mesna; Infusion of NK cells; Interleukin-2
Intervention description: 360 mg/m^2 once a day by vein on Day -4, Day -1 and Days 3, 6, 10, 13 and 17.; 25 mg/m^2 once a day by vein on Day -6 through Day -2 over 30 minutes.; 60 mg/kg once a day by vein on Days -5 and -4 over 2 hours.; 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.; Transplant of Haploidentical NK cells by vein on Day 0.; Subcutaneous injections three times a week for 9 doses on Days 0 to 21.
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Epratuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Healthy volunteers: No
Keywords: Blood And Marrow Transplantation; Relapsed Acute Lymphoblastic Leukemia; ALL; Leukemia; Pediatrics; Haploidentical NK cells; Cyclophosphamide; Cytoxan; Neosar; Epratuzumab; Fludarabine; Fludarabine Phosphate; Fludara; Interleukin-2; IL-2; Proleukin; Low-dose interleukin; Mesna; Mesnex; Natural Killer Cells; NK Cells Transplant

Summary:

      The goal of this clinical research study is to learn if transferring the donor's NK cells, in
      combination with an antibody called epratuzumab and low-dose interleukin (IL-2), into your
      body can be done safely. Researchers want to find out if the infused NK cells will survive
      after the infusion and if the NK cell infusion helps to destroy cancer cells in the
      recipient's body and possibly to help control the disease.

      Primary Objectives:

      · Evaluate the feasibility of collecting an adequate number of natural killer (NK) cells from
      a donor and evaluate the safety of a haploidentical donor-derived NK cell infusion,
      Epratuzumab, and low-dose interleukin-2 (IL-2).

      Secondary Objectives:

        -  Quantification and persistence of the infused donor NK cell in vivo;

        -  Quantification and persistence of cytokine levels;

        -  Assessment of NK cell immunophenotype and function;

        -  Correlate above with anti-tumor effect.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Recipient Inclusion criteria (within 28 days of this protocol's lymphodepleting
             conditioning regimen and after donor and recipient consent-signing)

          2. Diagnosis of CD22+ acute lymphoblastic leukemia that is a. refractory to therapy or b.
             in second or greater relapse without other standard therapeutic options

          3. Patient may have been the recipient of an allogeneic hematopoietic stem cell
             transplant; however; there must be no evidence of Graft-versus-host disease (GVHD)

          4. Off prednisone or other immunosuppressive medications for at least 3 days prior to
             both the lymphodepleting regimen and the NK infusion

          5. Zubrod performance scale </= 2 or Lansky performance scale >/= 60

          6. Adequate renal function defined as: Serum creatinine (Cr), for adults </= 2 mg/dL, for
             children </= 2 mg/dL or </= 2 times upper limit of normal (ULN) for age (whichever is
             less). If abnormal renal function, then Cr clearance >/= 60 mL/min/1.73 m^2

          7. Adequate liver function defined as: Total bilirubin </= 2 mg/dL and serum
             glutamic-pyruvic transaminase (SGPT)/ alanine transaminase(ALT) </= 5 * ULN for age
             (unless Gilbert's disease or abnormal liver function due to primary disease)

          8. Pulmonary symptoms controlled by medication and pulse oximetry >/= 92% room air

          9. Negative serum test to rule out pregnancy within 2 weeks prior to registration in
             females of childbearing potential (non childbearing is defined as greater than one
             year post-menopausal or surgically sterilized

         10. Requirement of sexually active females and males to use any form of contraception
             considered effective and medically acceptable by the Investigator. [Acceptable forms:
             birth control implants, birth control pills, a vasectomy (male surgical
             sterilization), or a double-barrier method (any 2 of the following in combination:
             intrauterine device (IUD), male or female condom with spermicidal gel, a diaphragm, a
             sponge, and/or cervical cap)]

         11. Negative serology for human immunodeficiency virus (HIV)

         12. Donor must be related to recipient and is predicted to be alloreactive based upon the
             presence of the relevant KIR genes and incompatibility with the recipient for HLA C or
             Bw antigens

         13. Donor must have infectious disease marker testing [Hepatitis B, C, HIV, CMV, Syphilis
             (RPR), Chagas, HTLV, and West Nile Virus] and CBC differential and platelet studies
             that meet standard medical eligibility criteria for allogeneic blood stem cell
             donation within 7 days of apheresis

         14. Donor, if a female of childbearing potential (non-childbearing is defined as greater
             than one year post-menopause or surgically sterilized), must have a negative serum
             test to rule out pregnancy within 14 days of apheresis

         15. Donor must meet standard medical eligibility criteria for allogeneic stem cell
             donation

        Exclusion Criteria:

          1. Exclusion criteria applies to both the initiation of conditioning regimen and to the
             NK infusion

          2. Active central nervous system (CNS) leukemia

          3. Active infection (defined as on antimicrobial therapy and or febrile)

          4. Breast-feeding females

          5. Currently using a ventilator or requiring supplemental oxygen

          6. Currently undergoing dialysis

          7. Currently using a Phase I, II, or III investigational agent. These agents should be
             stopped within 21 days of NK infusion

          8. New detected cardiac arrhythmia not controlled with medical management within prior 72
             hour period.

          9. Hypotension requiring pressor support within prior 72 hour period

         10. Uncontrolled infection defined as daily fever greater than or equal to 38.2°C within
             prior 24 hours and new positive culture for bacteria, fungus, or virus within 72 hours
             prior to NK -cell infusion, if clinically indicated

         11. Taking corticosteroids by mouth or intravenously within prior 72 hour period

         12. Ascites requiring paracentesis within prior 72 hour period. (If the patient requires
             paracentesis within 72 hours of NK cell infusion, they will not be eligible to receive
             the infusion.)

         13. Seizure activity or clinically detectable encephalopathy or new focal neurologic
             deficits within prior 72 hour period

         14. Donor has active infection (defined as on antimicrobial therapy and/or febrile) within
             7 days of apheresis

         15. Donor is pregnant female or breast-feeding female (within 7 days of apheresis)