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Trial Evaluating MGTA-456 in Patients With High-Risk Malignancy

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ClinicalTrials.gov Identifier: NCT03674411
Recruitment Status : Recruiting
First Posted : September 17, 2018
Last Update Posted : May 15, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is an single arm, open label, interventional phase II trial evaluating the efficacy of umbilical cord blood (UCB) hematopoietic stem and progenitor cells (HSPC) expanded in culture with stimulatory cytokines (SCF, Flt-3L, IL-6 and thromopoietin) on lympho-hematopoietic recovery. Patients will receive a uniform myeloablative conditioning and post-transplant immunoprophylaxis.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Lymphocytic Leukemia Biphenotypic/Undifferentiated Leukemia Chronic Myelogenous Leukemia Myelodysplasia Relapsed Large Cell Lymphoma Mantle Cell Lymphoma Hodgkin Lymphoma Burkitt Lymphoma Relapsed T-Cell Lymphoma Lymphoplasmacytic Lymphoma Drug: Fludarabine (FLU) Drug: Cyclophosphamide (CY) Drug: Total Body Irradiation (TBI) Drug: Tacrolimus (Tac) Drug: Mycophenolate Mofetil (MMF) Drug: Granulocyte Colony-Stimulating Factor (G-CSF) Drug: Busulfan (BU) Drug: Melphalan Drug: MGTA 456 Infusion Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-Arm, Open Label, Interventional Phase II Clinical Trial Evaluating MGTA-456 in Patients With High-Risk Malignancy
Actual Study Start Date : January 2, 2019
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : August 2023


Arm Intervention/treatment
Experimental: FLU, CY, TBI + MGTA-456 infusion Drug: Fludarabine (FLU)
25 mg/m2 IV over 1 hour (<10 kg: 0.83 mg/kg IV over 1 hour)

Drug: Cyclophosphamide (CY)
60 mg/kg IV over 2 hours

Drug: Total Body Irradiation (TBI)
165 cGy twice daily

Drug: Tacrolimus (Tac)
Tacrolimus will start day -3 and will be administered as a continuous IV infusion at a starting dose of 0.03 mg/kg/day. Goal trough levels will be 10-15 ng/mL for the first 14 days post-transplant and then decreased to a goal of 5-10 ng/ml thereafter.

Drug: Mycophenolate Mofetil (MMF)
MMF 3 gram/day IV/PO for adult patients divided in 2 or 3 doses. Pediatric patients will receive MMF at the dose of 15 mg/kg/dose (max 1 gram per dose) every 8 hours beginning day -3.

Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
5 ug/kg/d until the absolute neutrophil count (ANC) is >2500/uL for 2 consecutive days

Drug: MGTA 456 Infusion
The target cell dose is >10 x 106 CD34/kg with a maximum TNC 2.7 x 108/kg for children (<18 years) and 8.1 × 108 cells/kg [expanded product only] for adults based on the highest cell dose windows evaluated in prior studies.

Experimental: BU/ FLU/ MEL + MGTA-456 infusion Suspended: No Drug: Fludarabine (FLU)
25 mg/m2 IV over 1 hour (<10 kg: 0.83 mg/kg IV over 1 hour)

Drug: Tacrolimus (Tac)
Tacrolimus will start day -3 and will be administered as a continuous IV infusion at a starting dose of 0.03 mg/kg/day. Goal trough levels will be 10-15 ng/mL for the first 14 days post-transplant and then decreased to a goal of 5-10 ng/ml thereafter.

Drug: Mycophenolate Mofetil (MMF)
MMF 3 gram/day IV/PO for adult patients divided in 2 or 3 doses. Pediatric patients will receive MMF at the dose of 15 mg/kg/dose (max 1 gram per dose) every 8 hours beginning day -3.

Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
5 ug/kg/d until the absolute neutrophil count (ANC) is >2500/uL for 2 consecutive days

Drug: Busulfan (BU)
BU IV once daily with dose based on Pharmacokinetics (PK) calculator over 3 hours

Drug: Melphalan
50 mg/m2/day (1.7 mg/kg/day if < 10 kg) IV over 30 min

Drug: MGTA 456 Infusion
The target cell dose is >10 x 106 CD34/kg with a maximum TNC 2.7 x 108/kg for children (<18 years) and 8.1 × 108 cells/kg [expanded product only] for adults based on the highest cell dose windows evaluated in prior studies.




Primary Outcome Measures :
  1. Neutrophil Recovery [ Time Frame: Day 14 ]
    Incidence of neutrophil recovery by day 14 after transplantation in recipients of MGTA-456.


Secondary Outcome Measures :
  1. Hospitalization Rates [ Time Frame: Day 0 and Day 100 ]
    Number of days alive without hospitalization between days 0 and 100 after transplantation

  2. Secondary Graft Failure [ Time Frame: 2 Years ]
    Incidence of secondary graft failure

  3. Platelet Recovery [ Time Frame: Day 42 ]
    Incidence of platelet recovery at day 42

  4. Treatment Related Mortality (TRM) [ Time Frame: 6 Months ]
    Incidence of TRM at 6 months

  5. Grades II-IV Acute GVHD [ Time Frame: Day 100 ]
    Incidence of grades II-IV acute GVHD at day 100

  6. Grades III-IV Acute GVHD [ Time Frame: Day 100 ]
    Incidence of grades III-IV acute GVHD at day 100

  7. Chronic GVHD [ Time Frame: 1 Year ]
    Incidence of chronic GVHD at 1 year

  8. Relapse [ Time Frame: 2 Years ]
    Incidence of relapse at 2 years

  9. Non-catheter Associated Bacterial Infections [ Time Frame: Day 100 ]
    Incidence of non-catheter associated bacterial infections by day 100

  10. Overall Survival (OS) [ Time Frame: 2 Years ]
    Incidence of overall survival (OS) at 2 years

  11. Event-Free Survival (EFS) [ Time Frame: 2 Years ]
    Incidence of event-free survival (EFS) at 2 years



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Age, Unit Cell Dose and HLA Match Criteria

  • Subjects must be ≤55 years of age
  • Subjects must weigh >11 kg
  • Subjects must have a partially HLA matched UCB unit with a pre-cryopreserved TNC dose >1.0 x 107 per kilogram recipient weight. HLA matching is initially based on a minimum of 5 of 8 HLA alleles at high resolution A, B, C, DRB1 typing; searches will be performed according to the current Magenta Cord Blood Search Algorithm.

Eligible Diseases:

  • 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, eg. 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-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 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 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 (eg, 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) IPSS Int-2 or High risk (i.e. RAEB, RAEBt <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/PR that is ineligible for an autologous transplant.

Organ Specific Inclusion Criteria

  • Karnofsky score ≥70 (16 years and older), Lansky play score >50 (children 2-16 years, or 'adequate' score for children <2 years, as detailed in Appendix II.
  • Adequate organ function defined as:

    • Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then creatinine clearance >40 ml/min or GFR ≥70 mL/min/1.73 m2.normal for age
    • Hepatic: Bilirubin <3x upper limit of normal (ULN) and AST, ALT and alkaline phosphatase <5x ULN.
    • Pulmonary function: DLCO, FEV1, FEC (diffusion capacity) >5030% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation >95% on room air.
  • Cardiac: No uncontrolled arrhythmia and left ventricular ejection fraction at rest must be >3545%.
  • Available 'back-up' 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 >2 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 tostumomab (Bexxar), as part of their salvage therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03674411


Contacts
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Contact: Kim Nelson, RN 612-273-2925 knelso62@fairview.org

Locations
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United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Kim Nelson, RN    612-273-2925    knelso62@fairview.org   
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03674411     History of Changes
Other Study ID Numbers: 2018LS051
MT2018-06 ( Other Identifier: University of Minnesota Masonic Cancer Center )
First Posted: September 17, 2018    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Masonic Cancer Center, University of Minnesota:
AML
ALL
CML
MCL

Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Lymphoid
Leukemia, Myeloid
Hodgkin Disease
Lymphoma, Mantle-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma, T-Cell
Burkitt Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Preleukemia
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell