Donor Progenitor Cell and Natural Kill Cell Transplant in Treating Younger Patients with High-Risk Hematologic Malignancies
- Does not have a suitable human leukocyte antigen (HLA)-matched sibling donor (MSD) or volunteer HLA-matched unrelated donor (MUD) available in the necessary time for stem cell donation, or is not a candidate for MSD or MUD hematopoietic cell transplantation (HCT) due to refractory disease
- Has a suitable single haplotype matched (>= 3 of 6) family member donor
- High risk hematologic malignancy * High risk acute lymphoblastic leukemia (ALL) in complete remission 1 (CR1); examples include, but not limited to: t(9;22), hypodiploid, minimal residual disease (MRD) > 1% at the end of induction, M2 or greater marrow at the end of induction, infants with mixed-lineage leukemia (MLL) fusion or t(4;11) * ALL in high risk complete remission 2 (CR2); examples include, but not limited to t(9;22), bone marrow (BM) relapse < 36 months CR1, T-ALL, very early (< 6 months CR1) isolated central nervous system (CNS) relapse * ALL in complete remission 3 (CR3) or subsequent * Acute myeloid leukemia (AML) in high risk CR1 (diagnosis of AML includes myeloid sarcoma); examples include but not limited to: preceding myelodysplastic syndrome (MDS), 5q-, -5, -7, French-American-British Cooperative group (FAB) M6, FAB M7 not t(1;22), MRD > or = 5% on day 22 (AML08), MRD > 0.1% after two cycles of induction, M3 marrow after once cycle of induction, M2 marrow after two cycles of induction, fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) * AML in CR2 or subsequent * AML in relapse with < 25% blasts in BM * Therapy related AML, with prior malignancy in CR > 12 months * MDS, primary or secondary * 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 HCT, or unable to mobilize stem cells for autologous HCT * Non-Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize stem cells for autologous HCT * Juvenile myelomonocytic leukemia (JMML) * One of the following hematologic malignancies that are refractory (includes chemoresistant relapse or primary induction failure) ** ALL ** AML ** CML (blast crisis) ** Hodgkin or non-Hodgkin lymphoma
- If prior CNS leukemia, it must be treated and in CNS complete remission (CR)
- Does not have any other active malignancy other than the one for which this HCT is indicated
- No prior allogeneic HCT, and no autologous HCT within the previous 12 months
- Left ventricular ejection fraction > 40%, or shortening fraction >= 25%
- Creatinine clearance >= 50 ml/min/1.73m^2
- Forced vital capacity (FVC) >= 50% of predicted value; or pulse oximetry >= 92% on room air if patient is unable to perform pulmonary function testing
- Karnofsky or Lansky (age-dependent) performance score >= 50
- Bilirubin =< 3 times the upper limit of normal for age
- Alanine aminotransferase (ALT) =< 5 times the upper limit of normal for age
- Not pregnant; if female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment
- Not breast feeding
- Does not have current uncontrolled bacterial, fungal, or viral infection
- DONOR: At least single haplotype matched (>= 3 of 6) family member
- DONOR: At least 18 years of age
- DONOR: Human immunodeficiency virus (HIV) negative
- DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female)
- DONOR: Not breast feeding
- DONOR: Identified as either: * Completed the process of donor eligibility determination as outlined in 21 Code of Federal Regulations (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
I. To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus natural killer (NK) cell transplantation with total lymphoid irradiation (TLI) based conditioning regimen for high risk hematologic malignancy.
I. Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
II. Estimate incidence and severity of acute and chronic graft versus host disease (GVHD).
III. Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
I. Assess the relationship between pre-transplant minimal residual disease (MRD) with transplant outcomes.
II. Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) analysis, V-beta spectratyping, and lymphocyte phenotype and function.
III. Describe the use of cluster of differentiation (CD)45RA-depleted donor lymphocyte infusions (DLI) for recipients who have severe viral infections, disease recurrence or progression, or poor immune reconstitution.
IV. Assess and record efficacy of CD45RA-depleted DLI for these conditions, and all adverse events that are related to CD45RA-depleted DLI.
PREPARATIVE REGIMEN: Patients undergo TLI twice daily (BID) on day -9 and once daily (QD) days -8 and -7. Patients receive fludarabine phosphate intravenously (IV) QD on days -8 to -4, cyclophosphamide IV QD on day -6, thiotepa IV BID on day -3, and melphalan IV QD on days -2 and -1.
PROGENITOR CELLS: Patients receive allogeneic filgrastim-primed peripheral blood progenitor cells IV on days 0 and 1.
NK CELLS: Patients receive allogeneic CD56-positive CD3-negative natural killer cells IV on day 6.
After completion of study treatment, patients are followed up for 1 year.
Trial Phase Phase II
Trial Type Treatment
St. Jude Children's Research Hospital
Brandon Matthew Triplett
- Primary ID HAPNK1
- Secondary IDs NCI-2013-00609
- Clinicaltrials.gov ID NCT01807611