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

NCT ID: NCT03674411

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-02
• Study Completion Date: 2026-12-01

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FLU, CY, TBI + MGTA-456 infusion

All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.

All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and granulocyte-colony stimulating factor (G-CSF)

Group Type: EXPERIMENTAL

Fludarabine (FLU)

Intervention Type: DRUG

25 mg/m2 IV over 1 hour (\<10 kg: 0.83 mg/kg IV over 1 hour)

Cyclophosphamide (CY)

Intervention Type: DRUG

60 mg/kg IV over 2 hours

Total Body Irradiation (TBI)

Intervention Type: DRUG

165 cGy twice daily

Tacrolimus (Tac)

Intervention Type: DRUG

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.

Mycophenolate Mofetil (MMF)

Intervention Type: DRUG

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.

Granulocyte Colony-Stimulating Factor (G-CSF)

Intervention Type: DRUG

5 ug/kg/d until the absolute neutrophil count (ANC) is \>2500/uL for 2 consecutive days

MGTA 456 Infusion

Intervention Type: DRUG

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.

BU,FLU, MEL + MGTA-456 infusion

All young children \<3 years of age at the time of diagnosis will receive MGTA-456 on the day of transplantation after a non-TBI containing myeloablative conditioning as TBI may have a damaging effect on brain development in the very young child. All patients aged 0-3 years will be conditioned with busulfan (BU), FLU and melphalan (MEL) as well as Tac/MMF immunoprophylaxis and G-CSF

Group Type: EXPERIMENTAL

Fludarabine (FLU)

Intervention Type: DRUG

25 mg/m2 IV over 1 hour (\<10 kg: 0.83 mg/kg IV over 1 hour)

Mycophenolate Mofetil (MMF)

Intervention Type: DRUG

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.

Granulocyte Colony-Stimulating Factor (G-CSF)

Intervention Type: DRUG

5 ug/kg/d until the absolute neutrophil count (ANC) is \>2500/uL for 2 consecutive days

Busulfan (BU)

Intervention Type: DRUG

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

Melphalan

Intervention Type: DRUG

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

MGTA 456 Infusion

Intervention Type: DRUG

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.

Interventions

Fludarabine (FLU)

25 mg/m2 IV over 1 hour (\<10 kg: 0.83 mg/kg IV over 1 hour)

Intervention Type: DRUG

Cyclophosphamide (CY)

60 mg/kg IV over 2 hours

Intervention Type: DRUG

Total Body Irradiation (TBI)

165 cGy twice daily

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Granulocyte Colony-Stimulating Factor (G-CSF)

5 ug/kg/d until the absolute neutrophil count (ANC) is \>2500/uL for 2 consecutive days

Intervention Type: DRUG

Busulfan (BU)

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

Intervention Type: DRUG

Melphalan

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

• 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.

• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

MT2018-06

Identifier Type: OTHER

Identifier Source: secondary_id

2018LS051

Identifier Type: -

Identifier Source: org_study_id