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

This study has been completed.
Sponsor:
Collaborators:
Maastricht University Medical Center
Katholieke Universiteit Leuven
Information provided by (Responsible Party):
Yves Beguin, University Hospital of Liege
ClinicalTrials.gov Identifier:
NCT00603954
First received: January 2, 2008
Last updated: January 17, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Hematological Malignancies
Drug: Conditioning regimen TBI + Fludarabine
Drug: Conditioning regimen II (TLI 8 Gy + ATG [Thymoglobulin])
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Cell Transplantation With HLA-matched Donors : a Phase II Randomized Study Comparing 2 Nonmyeloablative Conditionings

Resource links provided by NLM:


Further study details as provided by University Hospital of Liege:

Primary Outcome Measures:
  • Grade II-IV acute GVHD between the 2 groups [ Time Frame: 180 days after HCT ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Hematopoietic (whole blood and T cell chimerism) engraftment and incidence of graft rejection in the 2 groups. [ Time Frame: 1 year after HCT ] [ Designated as safety issue: No ]
  • Incidence of grade I-IV and III-IV acute GVHD in the 2 groups [ Time Frame: 180 days after HCT ] [ Designated as safety issue: Yes ]
  • Incidence of chronic GVHD in the 2 groups [ Time Frame: 1 year after HCT ] [ Designated as safety issue: No ]
  • Quality and timing of immunologic reconstitution in the 2 groups [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • incidences of bacterial, fungal and viral infections in the 2 groups. [ Time Frame: 1 year after HCT ] [ Designated as safety issue: No ]
  • relapse rate, nonrelapse mortality, progression-free survival and overall survival in the 2 groups [ Time Frame: 1 year after HCT ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: December 2007
Study Completion Date: March 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
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
2 Gy TBI, Fludarabine 90 mg/m²
Active Comparator: 2
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 II (TLI 8 Gy + ATG [Thymoglobulin])
TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

PATIENT

  1. 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.
  2. Clinical situations

    • Theoretical indication for a standard allo-transplant, but not feasible because:

      • Age > 50 yrs;
      • Unacceptable end organ performance;
      • Patient's refusal.
    • Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.
  3. Other inclusion criteria

    • Male or female; fertile patients must use a reliable contraception method;
    • Age < 75 yrs;
    • Informed consent given by patient or his/her guardian if of minor age.

DONOR

  • Related to the recipient (sibling, parent or child) or unrelated;
  • Male or female;
  • Any age;
  • 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA allele matched;
  • Weight > 15 Kg (because of leukapheresis);
  • Fulfills criteria for allogeneic PBSC donation according to standard procedures;
  • Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures.

Exclusion Criteria:

PATIENT

  • Any condition not fulfilling inclusion criteria;
  • 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

  • Any condition not fulfilling inclusion criteria;
  • Unable to undergo leukapheresis because of poor vein access or other reasons.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00603954

Locations
Belgium
UZA
Edeghem, Antwerpen, Belgium
AZ Gasthuisberg Leuven
Leuven, Flamish Brabant, Belgium, 3000
UZ Gent
Gent, Flanders Oost, Belgium
University Hospital Mont-Godinne
Godinne, Namur, Belgium
AZ St-Jan
Brugge, West Flanders, Belgium
UZA Stuyvenberg
Antwerpen, Belgium
St Luc UCL
Brussels, Belgium
UZ Brussels
Brussels, Belgium
Bordet Institute
Brussels, Belgium
CHU Sart Tilman
Liege, Belgium, 4000
Netherlands
University Hospital Maastricht
Maastricht, Limburg, Netherlands, 6200
Sponsors and Collaborators
University Hospital of Liege
Maastricht University Medical Center
Katholieke Universiteit Leuven
Investigators
Study Chair: Frederic Baron, MD, PhD CHU-ULg
Study Chair: Yves Beguin, MD, PhD CHU-ULg
Principal Investigator: Johan Maertens, MD KUL
Principal Investigator: Koen Theunissen, MD KUL
Principal Investigator: Harry Schouten, MD Maastricht University Medical Center
  More Information

No publications provided

Responsible Party: Yves Beguin, Prof, University Hospital of Liege
ClinicalTrials.gov Identifier: NCT00603954     History of Changes
Other Study ID Numbers: TJB0702P1
Study First Received: January 2, 2008
Last Updated: January 17, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by University Hospital of Liege:
Nonmyeloablative conditioning.
Hematological malignancies.
GVHD.

Additional relevant MeSH terms:
Neoplasms
Fludarabine
Fludarabine phosphate
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014