IPA Targeted Adoptive Immunotherapy vs Adult Haplo-identical Cell Infusion During Induction of High Risk Leukemia
Condition: Acute Myeloid Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Myelodysplastic Syndromes
Intervention: haplo-identical cells (donor); umbilical cord blood unit (CBU)
Intervention description: Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment.; Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA. CBU grafts used in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x107 nucleated blood cells/kg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the overall safety of adoptive immunotherapy when
      given after chemotherapy for AML/MDS. Adoptive immunotherapy means using an infusion of cells
      from a donor to help fight cancer. The donor cells will be either from the umbilical cord
      blood (UCB) of a newborn baby or they will be cells collected from a relative
      (haplo-identical cells).

      The 2 cohorts that were discussed - adoptive immunotherapy with either UCB or haplo-identical
      stem cells - will be analyzed separately.

      Preliminary data from other centers has suggested that adoptive immunotherapy with cells from
      a relative is an effective approach that may improve remission rates and survival in AML and
      MDS, because they exert anti-cancer effects of their own (so called graft vs leukemia
      effects) and possibly because they hasten recovery of cell counts from chemotherapy. The
      Investigators are interested in confirming these data, but also in testing umbilical cord
      blood cells for the same purpose. Preliminary data indicate that umbilical cord blood cells
      may have more powerful graft vs leukemia effects and cause fewer side-effects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must be 18 years of age or older

          2. Patients with a confirmed diagnosis of AML or MDS, according to World Health
             Organization (WHO) classification (excluding acute promyelocytic leukaemia) with
             recurrent or refractory disease as defined below.

               1. For AML:

                    1. Primary induction failure (PIF) after ≥ 2 cycles of chemotherapy.

                    2. First relapse.

                    3. Relapse refractory to salvage chemotherapy

                    4. Second or subsequent relapse.

               2. For MDS, either refractory anemia with excess blasts (RAEB) I or RAEB II who
                  failed at least one chemotherapy regimen including either cytarabine or a
                  hypomethylating agent.

          3. Patients must have Karnofsky Performance score of ≥70

          4. Women of child-bearing potential must have a negative serum or urine pregnancy test
             within 2 weeks prior to treatment start

          5. Patients must be capable of understanding and complying with protocol requirements,
             and must be able and willing to sign a written informed consent form

        Exclusion Criteria:

          1. Persistent clinically significant toxicities from previous chemotherapy

          2. Known positive status for human immunodeficiency virus (HIV)

          3. Pregnant and nursing patients

          4. Uncontrolled intercurrent illness including, but not limited to, uncontrolled
             infection, or psychiatric illness/social situations that would limit compliance with
             study requirements

          5. Impairment of hepatic or renal function to such an extent that the patient, in the
             opinion of the investigator, will be exposed to an excessive risk if entered into this
             clinical study

          6. Active heart disease including myocardial infarction within previous 3 months,
             symptomatic coronary artery disease, arrhythmias not controlled by medication, or
             uncontrolled congestive heart failure. Any New York Heart Association (NYHA) grade 3
             or 4.

          7. Any medical condition which in the opinion of the investigator places the patient at
             an unacceptably high risk for toxicities