NCT01572181

Brief Summary

The purpose of this study is to assess transplant-related mortality (TRM) at one year after allogeneic hematopoietic stem cell transplantation (allo-HSCT) prepared by a "reduced toxicity myeloablative" conditioning regimen in young patients (children and adolescents) with hematologic malignancies.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
50

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2012

Longer than P75 for phase_2

Geographic Reach
1 country

15 active sites

Status
completed

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

First Submitted

Initial submission to the registry

February 21, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

April 1, 2012

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 6, 2012

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 24, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 24, 2017

Completed
Last Updated

April 5, 2018

Status Verified

April 1, 2018

Enrollment Period

5.6 years

First QC Date

February 21, 2012

Last Update Submit

April 4, 2018

Conditions

Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

  • Transplant-related mortality (TRM)

    Evaluation of the cumulative incidence of TRM at 12 months after transplantation

    12 months

Secondary Outcomes (5)

  • Incidence of engraftment

    Day+42

  • Evaluation of overall (OS) and disease-free survival (DFS)

    12 months

  • Cumulative incidence of relapse, death from disease, and non-relapse mortality (NRM)

    12 months

  • Cumulative incidences and severity of acute and chronic Graft-versus-Host disease

    12 months

  • Immune Recovery (to be determined in a subgroup of patients)

    12 months

Study Arms (1)

Drugs

EXPERIMENTAL

Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®)

Drug: Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®)

Interventions

Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®)DRUG

* IV fludarabine (30 mg/m²/day for 5 days) * IV Busulfan (Busilvex 3.2 mg/kg/day for 4 days) (the Busulfan dose is to be adapted to the weight of the child according to the drug label) * Anti-thymocyte globulines (Thymogolubuline, 2.5 mg/kg/day for 2 days).

Drugs

Eligibility Criteria

Age12 Months - 25 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Children and adolescents aged over 12 months and under 25 years
  • Availability of an HLA identical family donor or an HLA-matched unrelated donor (10/10 or 9/10 if the mismatch level is at HLACw for an unrelated donor) or availability of an HLA matched cord blood (5/6 or 6/6)
  • Informed consent signed by patients (18-25 years) and patient's legal representative, parent(s) or guardian (cf p13)
  • Diagnosis of a hematologic malignancy which is a candidate for allo-HSCT, but not eligible for standard or conventional myeloablative conditioning regimens because of high risk for toxicity.
  • Are considered as criteria of non-eligibility for standard or conventional myeloablative conditioning:
  • a history of autologous or allogeneic stem cell transplantation
  • comorbidities or medical history predictive of a prohibitive rate of TRM and toxicity with the use of standard high dose chemotherapy and / or radiotherapy.

You may not qualify if:

  • Patient has been administered any other systemic chemotherapeutic drug (including Gemtuzumab) within 21 days prior to trial enrollment and start of the conditioning regimen. Hydroxyurea is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease, that has been in remission for at least 3 months prior to enrollment on this study.
  • Active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.
  • Children and adolescents who are not older than 12 months and under 25 years
  • A donor who is HLA mismatched at the level of more than one locus.
  • Poor performance status (Lansky \< 50%)
  • Life expectancy is severely limited by concomitant illness and expected to be \<12 weeks.
  • Left ventricular ejection fraction \< 30%. Uncontrolled arrhythmias or symptomatic cardiac disease.
  • Symptomatic pulmonary disease. FEV1, FVC and DLCO \<30% of expected corrected for hemoglobin.
  • Creatinine clearance less than 30 mL/m per 1.73 m2 or requiring dialysis
  • Evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
  • Effusion or ascites \>1L prior to drainage.
  • HIV-positive.
  • Female pregnancy
  • Absence of effective contraception among boys and girls of childbearing potential (that contraception should be continued until 6 months after stopping treatment)
  • Breastfeeding
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

University Hospital

Besançon, France

Location

University Hospital

Bordeaux, France

Location

University Hospital

Clermont-Ferrand, France

Location

University Hospital

Grenoble, France

Location

University Hospital

Lille, France

Location

University Hospital

Lyon, France

Location

University Hospital

Marseille, France

Location

University Hospital

Montpellier, France

Location

University Hospital

Nancy, France

Location

University Hospital

Nantes, France

Location

University Hopsital

Paris, France

Location

University Hospital

Paris, France

Location

University Hospital

Rennes, France

Location

University Hopsital

Rouen, France

Location

University Hospital

Strasbourg, France

Location

Related Publications (1)

  • Rialland F, Grain A, Labopin M, Michel G, Gandemer V, Paillard C, Pochon C, Clement L, Brissot E, Jubert C, Sirvent A, Rohrlich PS, Plantaz D, Dalle JH, Mohty M. Reduced-toxicity myeloablative conditioning regimen using fludarabine and full doses of intravenous busulfan in pediatric patients not eligible for standard myeloablative conditioning regimens: Results of a multicenter prospective phase 2 trial. Bone Marrow Transplant. 2022 Nov;57(11):1698-1703. doi: 10.1038/s41409-022-01769-5. Epub 2022 Aug 26.

    PMID: 36028757DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

BusulfanAntilymphocyte Serum

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur CompoundsImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex Mixtures

Study Officials

  • Mohamad MOHTY, Professor

    Nantes University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

February 21, 2012

First Posted

April 6, 2012

Study Start

April 1, 2012

Primary Completion

October 24, 2017

Study Completion

October 24, 2017

Last Updated

April 5, 2018

Record last verified: 2018-04

Locations

FR(15)