Clinical trial NCT02199041 (phase 2, status: terminated)
Conditions: hematological malignancies
ICD codes: P61.9, P61.8, O28.0, T45.8X6S, T45.96XS, T45.8X3S, T45.8X4S
Drugs: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, mycophenolate mofetil, tacrolimus, methylprednisolone
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, CN(C)CCOC(C)(C1=CC=CC=C1)C1=CC=CC=N1, ClCCN(CCCl)P1(=O)NCCCO1, N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O, OS(=O)(=O)CCS, N[C@@H](CCCNC(N)=N)C(O)=O, COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O, [H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
Reason stopped: 
    the study was halted early due to slow accrual.
  
Eligibility criteria:

        Inclusion Criteria-Transplant Recipient:

          -  Age less than or equal to 21 years old.

          -  Does not have a suitable matched related/sibling donor (MSD) or volunteer matched
             unrelated donor (MUD) available in the necessary time for stem cell donation.

          -  Has a suitable partially human leukocyte antigen (HLA)-matched (≥ 3 of 6) family
             member donor.

          -  Has a partially HLA-matched single umbilical cord blood (UCB) unit (≥ 4 of 6) with
             adequate cell dose. UCB units must fulfill eligibility as outlined in 21 CFR 1271 and
             agency guidance.

          -  High-risk hematologic malignancy.

               -  High risk acute lymphocytic leukemia (ALL) in complete remission-1 (CR)1.
                  [Examples include, but not limited to t(9;22), hypodiploid,, M2 or greater marrow
                  at the end of induction, infants with mixed lineage leukemia (MLL) fusion or
                  t(4;11)].

               -  ALL in High risk CR2. [Examples include but not limited to t(9;22), bone marrow
                  (BM) relapse <36 mo CR1, T-ALL, very early (< 6mo CR1) isolated central nervous
                  system (CNS) relapse.]

               -  ALL in CR3 or subsequent.

               -  Acute myeloid leukemia (AML) in high risk CR1. [Examples include but not limited
                  to preceding MDS, 5q-, -5, -7, FAB M6, FAB M7 not t(1;22), minimal residual
                  disease (MRD) ≥ 5% on day 22 (AML08), M3 marrow after induction 1, M2 marrow
                  after two cycles of induction, FLT3-ITD.]

               -  AML in CR2 or subsequent.

               -  Therapy related AML, with prior malignancy in CR > 12mo

               -  Myelodysplastic syndrome (MDS), primary or secondary

               -  Natural killer (NK) cell, biphenotypic, or undifferentiated leukemia in CR1 or
                  subsequent.

               -  Chronic myeloid leukemia (CML) in accelerated phase, or in chronic phase with
                  persistent molecular positivity or intolerance to tyrosine kinase inhibitor.

               -  Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous
                  hematopoietic cell transplantation (HCT), or unable to mobilize stem cells for
                  autologous HCT.

               -  Non-Hodgkin lymphoma in CR2 or subsequent.

               -  Juvenile myelomonocytic leukemia (JMML).

               -  Refractory hematologic malignancies [ALL, AML, chronic myeloid leukemia (CML) in
                  blast crisis, Hodgkin or non-Hodgkin lymphoma] due to chemoresistant relapse or
                  primary induction failure.

               -  All patients with evidence of CNS leukemia must be treated and be in CNS CR to be
                  eligible for study.

          -  Patient must fulfill pre-transplant evaluation:

               -  Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 40% or shortening
                  fraction (SF) ≥ 25%.

               -  Creatinine clearance (CrCL) or glomerular filtration rate (GFR) ≥ 50
                  ml/min/1.73m2.

               -  Forced vital capacity (FVC) ≥ 50% of predicted value or pulse oximetry (Pox) ≥
                  92% on room air.

               -  Karnofsky or Lansky performance score ≥ 50.

               -  Bilirubin ≤ 3 times the upper limit of normal for age.

               -  Alanine aminotransferase (ALT) ≤ 5x the upper limit of normal for age.

               -  Aspartate aminotransferase (AST) ≤ 5x the upper limit of normal for age.

        Exclusion Criteria - Transplant Recipient:

          -  Patient has a suitable MSD, volunteer matched unrelated donor (MURD), or
             killer-immunoglobulin receptors (KIR) mismatched haploidentical donor available in the
             necessary time for stem cell donation.

          -  Patient has any other active malignancy other than the one for which HCT is indicated.

          -  Patient is pregnant as confirmed by positive serum or urine pregnancy test within 14
             days prior to enrollment.

          -  Patient is breast feeding.

          -  Patient has Down Syndrome.

          -  Patient has a current uncontrolled bacterial, fungal, or viral infection per the
             judgment of the principal investigator.

        Inclusion criteria - haploidentical donor

          -  At least single haplotype matched (≥ 3 of 6) family member

          -  At least 18 years of age.

          -  Human immunodeficiency virus (HIV) negative.

          -  Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days
             prior to enrollment (if female).

          -  Not breast feeding.

          -  Regarding eligibility, is identified as either:

               -  Completed the process of donor eligibility determination as outlined in 21 CFR
                  1271 and agency guidance; OR

               -  Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of
                  urgent medical need completed by the principal investigator or physician
                  sub-investigator per 21 CFR 1271.