Stem Cell Transplant with Chemotherapy and Selected Use of Blinatumomab in Treating Patients with Blood Cancer
- Does not have a suitable human leukocyte antigen (HLA)-matched sibling donor (MSD) or volunteer 10/10 HLA-matched unrelated donor (MUD) available in the necessary time for progenitor cell donation.
- Has a suitable single haplotype matched (>= 3 of 6) family member donor.
- High risk ALL in first complete remission (CR1). * Examples include, but not limited to: t(9;22) with persistent or recurrent transcript, hypodiploid cytogenetics, minimal residual disease (MRD) > 1% at the end of induction, M2 or greater marrow at the end of induction, recurrent or rising MRD after induction, infants with MLL fusion or t(4;11), relapse after prior chimeric antigen receptor T-cells (CART) therapy.
- ALL in High risk second complete remission (CR2). * Examples include, but not limited to t(9;22), bone marrow (BM) relapse < 36 months (mo) CR1 or < 6 mo after completion of therapy, any T-ALL, very early (< 6 mo CR1) isolated central nervous system (CNS) relapse, late BM relapse with poor response to standard reinduction therapy (e.g. MRD positive or recurrence after two blocks), relapse after prior CART therapy.
- ALL in third complete remission (CR3) or subsequent.
- AML in high risk CR1 (diagnosis of AML includes myeloid sarcoma). * Examples include but not limited to: preceding MDS or MDS-related AML, FAB M0, FAB M6, FAB M7 with high risk genetics such as ML not t(1;22), MRD > 0.1% after two cycles of induction, MRD > 1% after one cycle of induction, FLT3-ITD in combination with NUP98-NSD1 fusion or WT1 mutation, any high risk cytogenetics such as: DEK-NUP214 [t(6;9)], KAT6A-CREBBP [t(8;16)], RUNX1-CBFA2T3 [t(16;21)], -7, -5, 5q-, KMT2A-MLLT10 [t(6;11)], KMT2A-MLLT4 [t(10;11)], inv(3)(q21q26.2), CBFA2T3-GLIS2 [inv(16)(p13.3q24.3)], NUP98-KDM5A [t(11;12)(p15;p13)], ETV6-HLXB [t(7;12)(q36;p13)], NUP98-HOXA9 [t(7;11)(p15.4;p15)], NUP98-NSD1.
- AML in CR2 or subsequent.
- Therapy related AML, with prior malignancy in CR > 12 mo.
- Myelodysplastic syndrome (MDS), primary or secondary.
- Natural killer (NK) cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
- Chronic myelogenous 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 progenitor cells for autologous HCT.
- Non-Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize progenitor cells for autologous HCT.
- Juvenile myelomonocytic leukemia (JMML).
- If prior CNS leukemia, it must be treated and in CNS 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 (CrCl) or glomerular filtration rate (GFR) >= 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) aspartate aminotransferase (AST) =< 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.
- INCLUSION CRITERIA DOR HAPLOIDENTICAL DONOR: At least single haplotype matched (>= 3 of 6) family member.
- INCLUSION CRITERIA DOR HAPLOIDENTICAL DONOR: At least 18 years of age.
- INCLUSION CRITERIA DOR HAPLOIDENTICAL DONOR: Human immunodeficiency virus (HIV) negative.
- INCLUSION CRITERIA DOR HAPLOIDENTICAL DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
- INCLUSION CRITERIA DOR HAPLOIDENTICAL DONOR: Not breast feeding.
- INCLUSION CRITERIA DOR HAPLOIDENTICAL DONOR: Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
- INCLUSION CRITERIA DOR HAPLOIDENTICAL DONOR: 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. Determine the maximum effective dose for prophylactic CD45RA-depleted donor lymphocyte infusion (DLI) when given in the early post-engraftment period.
II. Assess the efficacy of T-cell receptor (TCR) alpha beta-depleted progenitor cell graft with additional memory T-cell DLI, plus selected use of blinatumomab, in haploidentical donor hematopoietic cell transplantation for hematologic malignancies as measured by 1 year event-free survival (EFS) (events = relapse, death).
I. Assess the safety and feasibility of the addition of blinatumomab in the early post-engraftment period in patients with CD19+ malignancy.
II. Estimate the incidence of neutrophil and platelet engraftment, malignant relapse, event-free survival per disease subgroups (e.g. acute lymphoblastic leukemia [ALL] versus [vs] acute myeloid leukemia [AML]), and overall survival at one-year post-transplantation.
III. Estimate incidence and severity of acute and chronic (graft versus host disease [GVHD]).
IV. Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
V. To measure and describe the pharmacokinetics of rabbit ATG in hematopoeitic cell transplantation (HCT) recipients on this study.
I. 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.
II. Describe the use of additional CD45RA-depleted DLI for recipients who have severe viral infections, disease recurrence or progression, or poor immune reconstitution.
III. Assess and record efficacy of CD45RA-depleted DLI for these conditions, and all adverse events that are related to CD45RA-depleted DLI.
Patients receive cyclophosphamide intravenously (IV) once daily (QD) on day -9, fludarabine phosphate IV QD on days -8 to -4, rabbit anti-thymocyte globulin IV daily over 2-6 hours on days -5 to -3, and melphalan IV QD on days -2 to -1. Patients also receive TCR alpha/beta positive (+) and CD19+ depleted hematopoietic progenitor cells IV on day 0 and may receive an additional dose on day 1. Patients receive filgrastim subcutaneously (SC) or IV daily for 2 consecutive days beginning on day 6. Beginning at least 2 weeks after engraftment, patients may receive CD45RA-depleted donor lymphocyte infusion IV. Patients with CD19+ malignancies also receive blinatumomab IV for 28 days beginning at least 1 week post-DLI.
After completion of study treatment, patients are followed up at days 21 and 100, at 1 year, and then annually for up to 10 years.
Trial Phase Phase II
Trial Type Treatment
Saint Jude Children's Research Hospital
Brandon Matthew Triplett
- Primary ID HAP2HCT
- Secondary IDs NCI-2019-00338
- Clinicaltrials.gov ID NCT03849651