Allogeneic HCT With HLA-matched Donors : a Phase II Randomized Study Comparing 2 Nonmyeloablative Conditionings

NCT00603954 | Completed Phase 2 Results

• 1 other identifier: TJB0702P1
• Study Type: interventional
• Target: 107
• Locations: 2 countries
• Sites: 11

Brief Summary

The present project aims at comparing two nonmyeloablative regimens currently used in 2 major HCT centers in the US for patients with HLA-matched related or unrelated donor: the one from the Seattle group consisting of 2 Gy TBI with fludarabine (90 mg/m²) versus the one from the Stanford group combining 8 Gy TLI with ATG.

Conditions

Hematological Malignancies

Keywords

Nonmyeloablative conditioning.; Hematological malignancies.; GVHD.

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Grade II-IV Acute GVHD Between the 2 Groups

  Percentage of participants with aGVHD according grades: Grade I: rash skin \< 25 % area; bilirubin: 20-30 mg/ml; diarrhea: 500-1000 ml/day Grade II: rash skin 25-50 % area; bilirubin: 30-60 mg/ml; diarrhea: 10000-1500 ml/day Grade III:rash skin \> 50 % area; bilirubin: 60-150 mg/ml; diarrhea: \>1500 ml/day Grade IV: erythroderma; bilirubin: \> 150 mg/ml; diarrhea: \>2000 ml/day Grade IV is the worst grade Patients given a second allogeneic HCT were censured for GVHD analyses.

  180 days after HCT

Secondary Outcomes (10)

• Number of Participants With Graft Rejection as Defined by Whole Blood and T Cell Chimerism

  1 year after HCT

• Percentage of Participants With Chronic GVHD in the 2 Groups

  2 years after HCT

• Incidences of Bacterial, Fungal and Viral Infections in the 2 Groups.

  D100 after HCT

• Percentage of Relapse Rate in the 2 Groups

  1 year after HCT

• Quality and Timing of Immunologic Reconstitution: Concentration of ATG Levels

  Day 0, Day 3 and Day 10

Study Arms (2)

TBI + fludarabine

ACTIVE COMPARATOR

Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.

Drug: Conditioning regimen: TBI + Fludarabine

TLI + ATG

ACTIVE COMPARATOR

Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.

Drug: Conditioning regimen:TLI (8 Gy) + ATG

Interventions

Conditioning regimen: TBI + Fludarabine DRUG

2 Gy TBI, Fludarabine 90 mg/m²

Also known as: total body irradiation (TBI) + fludarabine

TBI + fludarabine

Conditioning regimen:TLI (8 Gy) + ATG DRUG

TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg

Also known as: Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG)

TLI + ATG

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• PATIENT
• Diseases
• Hematological malignancies confirmed histologically and not rapidly progressing:
• AML in CR (defined as ≤ 5% marrow blasts and absence of blasts in the peripheral blood);
• MDS with ≤ 5% marrow blasts and absence of blasts in the peripheral blood;
• CML in CP;
• MPS not in blast crisis and not with extensive marrow fibrosis,
• ALL in CR;
• Multiple myeloma not rapidly progressing;
• CLL;
• Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
• Hodgkin's disease with chemosensitive disease.
• Clinical situations
• Theoretical indication for a standard allo-transplant, but not feasible because:
• Age \> 50 yrs;

You may not qualify if:

• PATIENT
• HIV positive;
• Non-hematological malignancy(ies) (except non-melanoma skin cancer) \< 3 years before nonmyeloablative HCT.
• Life expectancy severely limited by disease other than malignancy;
• Administration of cytotoxic agent(s) for "cytoreduction" within three weeks prior to initiating the nonmyeloablative transplant conditioning (Exceptions are hydroxyurea and imatinib mesylate);
• CNS involvement with disease refractory to intrathecal chemotherapy.
• Terminal organ failure, except for renal failure (dialysis acceptable)
• Uncontrolled infection;
• Karnofsky Performance Score \<70%;
• Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment;
• Patient is a female who is pregnant or breastfeeding;
• Previous radiation therapy precluding the use of 2 Gy TBI or 8 Gy TLI;
• DONOR
• Unable to undergo leukapheresis because of poor vein access or other reasons.

Sponsors & Collaborators

• University of Liege: lead
• Maastricht University Medical Center: collaborator
• KU Leuven: collaborator

Study Sites (11)

AZ Gasthuisberg Leuven

Leuven, Flamish Brabant, 3000, Belgium

Location

UZ Gent

Ghent, Flanders Oost, Belgium

Location

University Hospital Mont-Godinne

Godinne, Namur, Belgium

Location

AZ St-Jan

Bruges, West Flanders, Belgium

Location

UZA Stuyvenberg

Antwerp, Belgium

Location

UZA

Antwerp, Belgium

Location

Bordet Institute

Brussels, Belgium

Location

St Luc UCL

Brussels, Belgium

Location

UZ Brussels

Brussels, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

University Hospital Maastricht

Maastricht, Limburg, 6200, Netherlands

Location

Related Publications (2)

• Hannon M, Beguin Y, Ehx G, Servais S, Seidel L, Graux C, Maertens J, Kerre T, Daulne C, de Bock M, Fillet M, Ory A, Willems E, Gothot A, Humblet-Baron S, Baron F. Immune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation Following Flu-TBI versus TLI-ATG Conditioning. Clin Cancer Res. 2015 Jul 15;21(14):3131-9. doi: 10.1158/1078-0432.CCR-14-3374. Epub 2015 Mar 16.

  PMID: 25779951 DERIVED

• Baron F, Zachee P, Maertens J, Kerre T, Ory A, Seidel L, Graux C, Lewalle P, Van Gelder M, Theunissen K, Willems E, Emonds MP, De Becker A, Beguin Y. Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society. J Hematol Oncol. 2015 Feb 6;8:4. doi: 10.1186/s13045-014-0098-9.

  PMID: 25652604 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

fludarabine; Whole-Body Irradiation; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Frédéric Baron
• Organization: CHU de Liège

f.baron@ulg.ac.be

003243667201

Study Officials

• Frederic Baron, MD, PhD

  CHU-ULg

  STUDY CHAIR

• Yves Beguin, MD, PhD

  CHU-ULg

  STUDY CHAIR

• Johan Maertens, MD

  KUL

  PRINCIPAL INVESTIGATOR

• Koen Theunissen, MD

  KUL

  PRINCIPAL INVESTIGATOR

• Harry Schouten, MD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: January 2, 2008
• First Posted: January 29, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: January 26, 2022
• Results First Posted: January 26, 2022

Record last verified: 2021-11

Locations

NL (1); BE (10)