NCT02171104

Brief Summary

This single-institution, phase II study is designed to test the ability to achieve donor hematopoietic engraftment while maintaining low rates of transplant-related mortality (TRM) using busulfan- and fludarabine-based conditioning regimens with busulfan therapeutic drug monitoring (TDM) for patients with various inherited metabolic disorders (IMD) and severe osteopetrosis (OP).

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
149

participants targeted

Target at P75+ for phase_2

Timeline
39mo left

Started Jul 2014

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress79%
Jul 2014Jul 2029

First Submitted

Initial submission to the registry

June 20, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 23, 2014

Completed
17 days until next milestone

Study Start

First participant enrolled

July 10, 2014

Completed
11.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 5, 2026

Completed
3.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 14, 2029

Expected
Last Updated

January 7, 2026

Status Verified

January 1, 2026

Enrollment Period

11.5 years

First QC Date

June 20, 2014

Last Update Submit

January 5, 2026

Conditions

Keywords

allogeneic hematopoietic cell transplantationbone marrow transplantationIMDAMACRDMNGIEHDLSOPALD

Outcome Measures

Primary Outcomes (2)

  • Percent of subjects who achieve high-level donor hematopoietic engraftment

    Defined as neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant

    Day +42 post-transplant

  • Percent of subjects who achieve high-level donor hematopoietic engraftment

    Defined as ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant

    Day +100 post-transplant

Secondary Outcomes (5)

  • Graft-versus-host disease

    Day +100 post-transplant

  • Transplant-related mortality

    Day +100 post-transplant

  • Regimen-related toxicity

    Day +100 post-transplant

  • Post-HSCT changes in disease

    1 year

  • Post-HSCT changes in disease

    2 years

Study Arms (7)

IMD - Except Haplo-identical

EXPERIMENTAL

Inherited Metabolic Disease (IMD) - Except Haplo-Identical See intervention descriptions.

Biological: Stem Cell TransplantationDrug: IMD Preparative Regimen

OP - Except Haplo-Identical

EXPERIMENTAL

Severe Osteoperosis (OP) - Except Haplo-Identical See intervention descriptions.

Biological: Stem Cell TransplantationDrug: Osteopetrosis Only Preparative Regimen

OP and IMD -Haplo-Identical Only

EXPERIMENTAL

Severe Osteopetrosis (OP) and Inhterited Metabolic Disorders (IMD) -Haplo-Identical Only See intervention descriptions.

Biological: Stem Cell TransplantationDrug: Osteopetrosis Haploidentical Only Preparative Regimen

cALD SR-A (Standard-Risk, Regimen A)

EXPERIMENTAL

See intervention descriptions.

Biological: Stem Cell TransplantationDrug: IMD Preparative RegimenDrug: cALD SR-A (Standard-Risk, Regimen A)

cALD SR-B (Standard-Risk, Regimen B)

EXPERIMENTAL

See intervention descriptions.

Biological: Stem Cell TransplantationDrug: IMD Preparative RegimenDrug: cALD SR-B (Standard-Risk, Regimen B)

cALD HR-C (High-Risk, Regimen C)

EXPERIMENTAL

See intervention descriptions.

Biological: Stem Cell TransplantationDrug: IMD Preparative RegimenDrug: cALD HR-D (High-Risk, Regimen C)

cALD HR-D (High-Risk, Regimen D)

EXPERIMENTAL

See intervention descriptions.

Biological: Stem Cell TransplantationDrug: IMD Preparative RegimenDrug: cALD HR-D (High-Risk, Regimen D)

Interventions

Infusion given on Day 0

IMD - Except Haplo-identicalOP - Except Haplo-IdenticalOP and IMD -Haplo-Identical OnlycALD HR-C (High-Risk, Regimen C)cALD HR-D (High-Risk, Regimen D)cALD SR-A (Standard-Risk, Regimen A)cALD SR-B (Standard-Risk, Regimen B)

* Anti-thymocyte Globulin (ATG) * Fludarabine * Busulfan

IMD - Except Haplo-identicalcALD HR-C (High-Risk, Regimen C)cALD HR-D (High-Risk, Regimen D)cALD SR-A (Standard-Risk, Regimen A)cALD SR-B (Standard-Risk, Regimen B)

* Anti-thymocyte Globulin (ATG) * Fludarabine * Busulfan * Thiotepa

OP - Except Haplo-Identical

* Rituximab * Alemtuzumab * Busulfan * Fludarabine

OP and IMD -Haplo-Identical Only

N-acetylcysteine start day +1 through day +28

cALD SR-A (Standard-Risk, Regimen A)

N-acetylcysteine start day +1through day +56

cALD SR-B (Standard-Risk, Regimen B)

N-acetylcysteine and celecoxib start day of admission (prior to conditioning regimen) and continue through day +100

cALD HR-C (High-Risk, Regimen C)

N-acetylcysteine, celecoxib, vitamin E and alpha lipoic acid start day of admission (prior to conditioning regimen) and continue through day +100

cALD HR-D (High-Risk, Regimen D)

Eligibility Criteria

AgeUp to 55 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • through 55 years of age
  • Adequate graft available
  • Adequate organ function
  • Eligible Diseases:
  • Mucopolysaccharidosis Disorders:
  • MPS IH (Hurler syndrome)
  • MPS II (Hunter syndrome) if the patient has no or minimal evidence of symptomatic neurologic disease but is expected to have a neurologic phenotype
  • MPS VI (Maroteaux-Lamy syndrome)
  • MPS VII (Sly syndrome)
  • Glycoprotein Metabolic Disorders:
  • Alpha mannosidosis
  • Fucosidosis
  • Aspartylglucosaminuria
  • Sphingolipidoses and Recessive Leukodystrophies:
  • Globoid cell leukodystrophy
  • +17 more criteria

You may not qualify if:

  • Pregnancy - menstruating females must have a negative serum or urine pregnancy test within 14 days of study treatment start
  • Prior myeloablative chemotherapy exposure within 4 months of the start of conditioning on this protocol (patients excluded for this reason may be eligible for other institutional protocols)
  • Uncontrolled bacterial, fungal or viral infections including HIV (including active infection with Aspergillus or other mold within 30 days)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis IMucopolysaccharidosis IIMucopolysaccharidosis VIMucopolysaccharidosis VIIalpha-MannosidosisFucosidosisAspartylglucosaminuriaSphingolipidosesLeukodystrophy, Globoid CellLeukodystrophy, MetachromaticPeroxisomal DisordersZellweger SyndromeRefsum Disease, InfantilePeroxisomal ACYL-COA oxidase deficiencyPseudo-Zellweger syndromeOsteopetrosisHereditary Diffuse Leukoencephalopathy with SpheroidsAlpha-Methylacyl-CoA Racemase Deficiency

Interventions

Stem Cell TransplantationRegimen B

Condition Hierarchy (Ancestors)

MucopolysaccharidosesCarbohydrate Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLysosomal Storage DiseasesMucinosesConnective Tissue DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesX-Linked Intellectual DisabilityIntellectual DisabilityNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesGenetic Diseases, X-LinkedHeredodegenerative Disorders, Nervous SystemMannosidase Deficiency DiseasesLysosomal Storage Diseases, Nervous SystemBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesLipidosesLipid Metabolism, Inborn ErrorsLipid Metabolism DisordersHereditary Central Nervous System Demyelinating DiseasesLeukoencephalopathiesDemyelinating DiseasesSulfatidosisLiver DiseasesDigestive System DiseasesKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesAbnormalities, MultipleCongenital AbnormalitiesOsteosclerosisOsteochondrodysplasiasBone Diseases, DevelopmentalBone DiseasesMusculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Cell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Study Officials

  • Paul Orchard, M.D.

    Masonic Cancer Center, University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

June 20, 2014

First Posted

June 23, 2014

Study Start

July 10, 2014

Primary Completion

January 5, 2026

Study Completion (Estimated)

July 14, 2029

Last Updated

January 7, 2026

Record last verified: 2026-01

Locations