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

NCT03674411 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 2018LS051MT2018-06
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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; Myelodysplasia; Acute Lymphocytic Leukemia; Biphenotypic/Undifferentiated Leukemia; Chronic Myelogenous Leukemia; Relapsed Large Cell Lymphoma; Mantle Cell Lymphoma; Hodgkin Lymphoma; Burkitt Lymphoma; Relapsed T-Cell Lymphoma; Lymphoplasmacytic Lymphoma

Keywords

AML; ALL; CML; MCL

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Neutrophil Recover

  Percentage of participants with neutrophil recovery by day 14 after transplantation in recipients of MGTA-456.

  Day 14

Secondary Outcomes (11)

• Number of Days Alive Without Hospitalization

  Day 0 and Day 100

• Secondary Graft Failure

  2 Years

• Platelet Recovery

  Day 42

• Treatment Related Mortality (TRM)

  6 Months

• Grades II-IV Acute GVHD

  Day 100

Study Arms (2)

FLU, CY, TBI + MGTA-456 infusion

EXPERIMENTAL

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)

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: MGTA 456 Infusion

BU,FLU, MEL + MGTA-456 infusion

EXPERIMENTAL

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

Drug: Fludarabine (FLU); Drug: Mycophenolate Mofetil (MMF); Drug: Granulocyte Colony-Stimulating Factor (G-CSF); Drug: Busulfan (BU); Drug: Melphalan; Drug: MGTA 456 Infusion

Interventions

Fludarabine (FLU) DRUG

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

BU,FLU, MEL + MGTA-456 infusion; FLU, CY, TBI + MGTA-456 infusion

Cyclophosphamide (CY) DRUG

60 mg/kg IV over 2 hours

FLU, CY, TBI + MGTA-456 infusion

Total Body Irradiation (TBI) DRUG

165 cGy twice daily

FLU, CY, TBI + MGTA-456 infusion

Tacrolimus (Tac) 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.

FLU, CY, TBI + MGTA-456 infusion

Mycophenolate Mofetil (MMF) 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.

BU,FLU, MEL + MGTA-456 infusion; FLU, CY, TBI + MGTA-456 infusion

Granulocyte Colony-Stimulating Factor (G-CSF) DRUG

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

BU,FLU, MEL + MGTA-456 infusion; FLU, CY, TBI + MGTA-456 infusion

Busulfan (BU) DRUG

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

BU,FLU, MEL + MGTA-456 infusion

Melphalan DRUG

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

BU,FLU, MEL + MGTA-456 infusion

MGTA 456 Infusion 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; FLU, CY, TBI + MGTA-456 infusion

Eligibility Criteria

• Age: Up to 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Anemia, Refractory, with Excess of Blasts; Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Mantle-Cell; Hodgkin Disease; Burkitt Lymphoma; Lymphoma, T-Cell; Lymphoma, B-Cell, Marginal Zone

Interventions

fludarabine; Cyclophosphamide; Whole-Body Irradiation; Tacrolimus; Triamcinolone; Mycophenolic Acid; Granulocyte Colony-Stimulating Factor; Busulfan; Melphalan

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Histiocytic Disorders, Malignant; Histiocytosis; Lymphoma, Non-Hodgkin; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Results Point of Contact

• Title: Dr. Margaret MacMillan
• Organization: University of Minnesota, Masonic Cancer Center

macmi002@umn.edu

(612) 626-5654

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2018
• First Posted: September 17, 2018
• Study Start: January 2, 2019
• Primary Completion: June 23, 2020
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 6, 2026
• Results First Posted: January 30, 2024

Record last verified: 2025-12

Locations

US (1)