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

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03674411
Collaborator
(none)
22
1
2
54.9
0.4

Study Details

Study Description

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
  • 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

Study Design

Study Type:
Interventional
Actual Enrollment :
22 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 :
Jan 2, 2019
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Neutrophil Recovery [Day 14]

    Incidence of neutrophil recovery by day 14 after transplantation in recipients of MGTA-456.

Secondary Outcome Measures

  1. Hospitalization Rates [Day 0 and Day 100]

    Number of days alive without hospitalization between days 0 and 100 after transplantation

  2. Secondary Graft Failure [2 Years]

    Incidence of secondary graft failure

  3. Platelet Recovery [Day 42]

    Incidence of platelet recovery at day 42

  4. Treatment Related Mortality (TRM) [6 Months]

    Incidence of TRM at 6 months

  5. Grades II-IV Acute GVHD [Day 100]

    Incidence of grades II-IV acute GVHD at day 100

  6. Grades III-IV Acute GVHD [Day 100]

    Incidence of grades III-IV acute GVHD at day 100

  7. Chronic GVHD [1 Year]

    Incidence of chronic GVHD at 1 year

  8. Relapse [2 Years]

    Incidence of relapse at 2 years

  9. Non-catheter Associated Bacterial Infections [Day 100]

    Incidence of non-catheter associated bacterial infections by day 100

  10. Overall Survival (OS) [2 Years]

    Incidence of overall survival (OS) at 2 years

  11. Event-Free Survival (EFS) [2 Years]

    Incidence of event-free survival (EFS) at 2 years

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Masonic Cancer Center at University of Minnesota Minneapolis Minnesota United States 55455

Sponsors and Collaborators

  • Masonic Cancer Center, University of Minnesota

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT03674411
Other Study ID Numbers:
  • 2018LS051
  • MT2018-06
First Posted:
Sep 17, 2018
Last Update Posted:
Aug 16, 2021
Last Verified:
Aug 1, 2021
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 16, 2021