Laboratory Expanded Umbilical Cord Blood Product (Spanlecortemlocel) in Treating Patients with High-Risk Blood Cancers

Status: Active

Description

This phase II trial studies how the transplantation of laboratory expanded cord blood, called spanlecortemlocel, works in treating patients with high-risk blood cancers. Umbilical cord blood transplantation has been primarily used in patients with blood cancers. However, the blood counts are slower to recover after this type of transplantation, which can result in a longer hospital stays and a greater number of transfusions. To speed up blood count recovery, the number of blood forming stem cells can be multiplied more than 300 times on average in the laboratory prior to transfusion. Using spanlecortemlocel may speed up blood count recovery in patients with high-risk blood cancers.

Eligibility Criteria

Inclusion Criteria

  • Subjects must weigh > 11 kg.
  • Subjects must have a partially human leukocyte antigen (HLA) matched UCB unit with a pre-cryopreserved total nucleated cell (TNC) dose > 1.0 x 10^7 per kilogram recipient weight. HLA matching is initially based on a minimum of 4 of 6 HLA-A and B (at low or intermediate resolution by molecular typing) and DRB1 (at high resolution by molecular typing); searches will be performed according to the Magenta Cord Blood Search Algorithm.
  • Acute myelogenous leukemia (AML) in morphological complete remission with: * Minimal residual disease (MRD) by flow cytometry, or * Intermediate to high risk leukemia in first (CR1) based on institutional criteria, e.g. not favorable risk AML which is defined as having one of the following: ** T(8,21) without cKIT mutation. ** Inv(16) or t(16;16) without cKIT mutation. ** Normal karyotype with mutated NPM1 but FLT3-internal tandem duplication (ITD) wild type. ** Normal karyotype with double mutated CEBPA. ** Acute promyelocytic leukemia (APL) in first molecular remission at the end of consolidation. * Any second or subsequent complete remission (CR), or * Secondary AML with prior malignancy that has been in remission for at least 12 months.
  • Acute lymphocytic leukemia (ALL) at the following stages: * High risk first morphological, cytogenetic and molecular CR with: ** MRD by flow cytometry, or ** Diagnosis of Philadelphia chromosome (Ph)+ ALL, or ** MLL rearrangement at diagnosis with slow early response at Day 14, or ** Hypodiploidy (< 44 chromosomes or deoxyribonucleic acid [DNA] index < 0.81) at diagnosis, or. ** End of induction M3 bone marrow, or ** End of induction M2 with M2-3 at Day 42 * High risk second CR based on institutional criteria (e.g., for children, bone marrow relapse < 36 months from induction or T-lineage bone marrow relapse or very early isolated central nervous system (CNS) relapse < 6 months from diagnosis, or slow re-induction (stage M2-3 at day 28 after induction) regardless of length remission. All patients with MRD by flow cytometry. * Any third or subsequent CR.
  • Secondary ALL.
  • Biphenotypic/undifferentiated leukemia in morphological, cytogenetic and molecular CR.
  • Chronic Myelogenous Leukemia (CML) in high risk first chronic phase (failure of two tyrosine kinase inhibitors [TKI] or TKI intolerance), accelerated phase or second chronic phase.
  • Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e. refractory anemia with excess blasts [RAEB], RAEB in transformation [t] < 5% blasts) or other high risk features, including multiple cytopenias, high risk cytogenetics or lack of response to standard therapy.
  • Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma that is chemotherapy sensitive and ineligible for an autologous transplant.
  • Burkitt’s lymphoma in CR2 or subsequent CR.
  • Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/partial remission (PR) that is ineligible for an autologous transplant.
  • Karnofsky score >= 70 (16 years and older), Lansky play score >= 50 (children 2-16 years, or ‘adequate’ score for children < 2 years.
  • Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then creatinine clearance > 40 ml/min or glomerular filtration rate (GFR) normal for age.
  • Bilirubin < 3 x upper limit of normal (ULN).
  • Aspartate aminotransferase (AST) < 5 x ULN.
  • Alanine aminotransferase (ALT) < 5 x ULN.
  • Alkaline phosphatase < 5 x ULN.
  • Diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), FEC (diffusion capacity) > 50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2) saturation > 95% on room air.
  • No uncontrolled arrhythmia and left ventricular ejection fraction at rest must be > 45%.
  • Available ‘back-up’ hematopoietic stem and progenitor cells (HSPC) graft (e.g., second UCB unit, haploidentical related donor).
  • Females of child bearing potential and sexually active males must agree to use adequate birth control during study treatment.
  • Voluntary written consent signed (adult or parental) before performance of any study-related procedure not part of normal medical care.

Exclusion Criteria

  • Patients with a HLA matched sibling donor or a HLA matched unrelated donor who is available for marrow or peripheral blood stem cell collection at the desired time of transplant.
  • Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy.
  • Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology.
  • Active bacterial, viral or fungal infection (currently taking medication and persistence of clinical signs and symptoms) with a minimum of 4 weeks of anti-fungal treatment.
  • Prior autologous or allogeneic transplant.
  • Other active malignancy.
  • Subjects > 3 years of age unable to receive TBI 1320 cGy due to extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation, or prior Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar), as part of their salvage therapy.

Locations & Contacts

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Heather E. Stefanski
Phone: 612-626-2961
Email: stef0030@umn.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES

I. Determine if transplantation of spanlecortemlocel (MGTA-456) significantly reduces the expected duration of neutropenia and number of hospital days to day 100 relative to that observed in recipients of an unmanipulated single umbilical cord blood (UCB) unit.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I (AGE 3-55 YEARS): Patients receive fludarabine intravenously (IV) over 1 hour on days -8 to -6 and cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total-body irradiation (TBI) twice daily (BID) on days -4 to -1, and receive tacrolimus IV on days -3 to 100 and tapered till day 180, and mycophenolate mofetil (MMF) IV or orally (PO) every 8 hours starting on days -3 to 30 or 7 days after absolute neutrophil count (ANC) is > 0.5 x 10^9 /L. Patients then receive spanlecortemlocel IV over 30 minutes on day 0. Beginning day 1, patients also receive granulocyte colony-stimulating factor (G-CSF) IV.

GROUP II (Age =< 3 YEARS): Patients receive busulfan IV over 3 hours once daily (QD) on days -8 to -5, fludarabine IV over 1 hour and melphalan IV over 30 minutes on days -4 to -2. Patients also receive tacrolimus IV on days -3 to 100 and tapered till day 180, and MMF IV or PO every 8 hours starting on days -3 to 30 or 7 days after ANC is > 0.5 x 10^9 /L. Patients then receive spanlecortemlocel IV over 30 minutes on day 0 and G-CSF IV on day 1.

After completion of study treatment, patients are followed up on days 7, 14, 21, 28, 35, 42, 60, 100, 180, 360, and 720.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Heather E. Stefanski

Trial IDs

Primary ID 2018LS051
Secondary IDs NCI-2018-02305, MT2018-06
Clinicaltrials.gov ID NCT03674411