Allogeneic HCT With HLA-matched Donors : a Phase II Randomized Study Comparing 2 Nonmyeloablative Conditionings
Condition: Hematological Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: Conditioning regimen: TBI + Fludarabine; Conditioning regimen:TLI (8 Gy) + ATG
Intervention description: 2 Gy TBI, Fludarabine 90 mg/m²; TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 107.0
Sex: All
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Nonmyeloablative conditioning.; Hematological malignancies.; GVHD.

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.
    

Eligibility 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.