Clinical Trials /

Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases

NCT02145039

Description:

This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen, consisting of fludarabine, cyclophosphamide and low dose total body irradiation (TBI), is designed for the treatment of patients with advanced and/or high risk diseases.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Acute Promyelocytic Leukemia
  • Adult T-Cell Leukemia/Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Chronic Myeloid Leukemia
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Mature T-Cell and NK-Cell Lymphoma/Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasm
  • Prolymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Reduced Intensity Conditioning and Haploidentical Related Bone Marrow for Patients With Hematologic Diseases
  • Official Title: Reduced Intensity Conditioning (RIC) and Transplantation of HLA-Haploidentical Related Bone Marrow (Haplo-BM) For Patients With Hematologic Diseases

Clinical Trial IDs

  • ORG STUDY ID: 2013OC116
  • SECONDARY ID: MT2013-33C
  • NCT ID: NCT02145039

Conditions

  • Acute Leukemias
  • Burkitt's Lymphoma
  • Chronic Myelogenous Leukemia

Interventions

DrugSynonymsArms
FludarabineFludaraHaploidentical stem cell transplant
CyclophosphamideHaploidentical stem cell transplant
Haploidentical stem cell transplantHSCTHaploidentical stem cell transplant

Purpose

This is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen, consisting of fludarabine, cyclophosphamide and low dose total body irradiation (TBI), is designed for the treatment of patients with advanced and/or high risk diseases.

Trial Arms

NameTypeDescriptionInterventions
Haploidentical stem cell transplantExperimentalThis is a treatment guideline for HLA-Haploidentical hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) regimen. This regimen consists of fludarabine, cyclophosphamide and low dose total body irradiation (TBI).
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          -  Must be <75 years old with no 7/8 or 8/8 HLA-matched sibling donor

          -  One or more potential related mismatched donors (e.g. biologic parent (s) or siblings
             (full or half) or children). Low resolution using DNA based typing at HLA-A, -B and
             -DRB1 for potential haploidentical donors is required.

          -  All diseases listed below are advanced hematologic malignancies not curable by
             conventional chemotherapy. Responses to conventional treatment range from zero to 30%
             but are typically short lived.

               -  Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT
                  considered favorable-risk.

               -  Acute Myelogenous Leukemia (AML) in first complete remission (CR1) that is NOT
                  considered as favorable-risk.

               -  Acute Leukemias in 2nd or subsequent CR

               -  Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR,
                  adult T-cell leukemia/lymphoma in first or subsequent CR

               -  Burkitt's lymphoma in CR2 or subsequent CR

               -  Natural killer cell malignancies after response to initial therapy

               -  Chronic myelogenous leukemia: all types except refractory blast crisis.

               -  Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy
                  sensitive disease that has failed or patients who are ineligible for an
                  autologous transplant.

               -  Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone
                  B-cell lymphoma, follicular lymphoma, which have progressed within 12 months of
                  achieving a partial or complete remission.

               -  Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are
                  eligible after initial therapy if chemotherapy sensitive.

               -  Refractory leukemia or MDS These patients may be taken to transplant in aplasia
                  after induction or re-induction chemotherapy or radiolabeled antibody.

               -  Bone marrow failure syndromes, except for Fanconi Anemia

               -  Myeloproliferative syndromes

          -  Adequate organ function is defined as:

               -  Cardiac: Absence of decompensated congestive heart failure, or uncontrolled
                  arrhythmia and left ventricular ejection fraction > 35%. For children that are
                  not able to cooperate with MUGA and echocardiography, such should be clearly
                  stated in the physician's note

               -  Pulmonary: DLCO > 30% predicted, and absence of O2 requirements. For children
                  that are not able to cooperate with PFTs, a pulse oximetry with exercise should
                  be attempted. If nether test can be obtained it should be clearly stated in the
                  physician's note.

               -  Liver: Transaminases < 5 x upper limit of normal and bilirubin < 3 x upper limit
                  of normal

               -  Renal: serum creatinine < 2.0 mg/dl (adults) or glomerular filtration rate (GFR)
                  >40 mL/min/1.73m2 (peds). Patients with a creatinine > 1.2 mg/dl or a history of
                  renal dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2.

               -  Adequate performance status is defined as Karnofsky score ≥ 60% (> 16 years of
                  age) or Lansky score ≥ 50 (pediatrics)

          -  If recent mold infection e.g. Aspergillus - must have minimum of 30 days of
             appropriate treatment before BMT and infection controlled and be cleared by Infectious
             Disease.

          -  Second BMT: Must be > 3 months after prior myeloablative transplant.

          -  Patients must be ineligible for autologous transplantation due to prior autologous
             transplant, an inadequate autologous stem cell harvest, inability to withstand a
             myeloablative preparative regimen, or clinically aggressive/high risk disease.

          -  Patients are eligible for transplantation if there is no evidence of progressive
             disease by imaging modalities or biopsy. Persistent PET activity, though possibly
             related to lymphoma, is not an exclusion criterion in the absence of CT changes
             indicating progression.

          -  Patients with stable disease are eligible for transplantation if the largest residual
             nodal mass is < 5 cm (approximately). For patients who have responded to preceding
             therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm
             (approximately).

          -  Voluntary written consent (adult or parental/guardian)

        Exclusion Criteria:

          -  Available and clinically suitable 5-6/6 HLA-A, B, DRB1 matched sibling donor

          -  Pregnant or breastfeeding

          -  Evidence of HIV infection or known HIV positive serology

          -  Current active serious infection

          -  Unless in post-chemotherapy and radioimmunoconjugated antibody induced aplasia, when
             he/she would be eligible, patients with acute leukemia in morphologic relapse/
             persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts
             if blasts have unique morphologic markers (e.g. Auer rods) or associated cytogenetic
             markers that allows morphologic relapse to be distinguished are not eligible.

          -  CML in refractory blast crisis

          -  Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on
             salvage therapy. Stable disease is acceptable to move forward provided it is
             non-bulky.

          -  active central nervous system malignancy
      
Maximum Eligible Age:74 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:2 year survival
Time Frame:2 years
Safety Issue:
Description:Proportion of patients that survive 2 years post-transplant

Secondary Outcome Measures

Measure:Incidence of hematopoietic engraftment
Time Frame:42 days
Safety Issue:
Description:
Measure:Incidence of chimerism
Time Frame:1 year
Safety Issue:
Description:Incidence of chimerism at day 100, 6 months and 1 year
Measure:Incidence of acute GVHD at 100 days
Time Frame:100 days
Safety Issue:
Description:
Measure:Incidence of chronic GVHD at 1 year
Time Frame:1 year
Safety Issue:
Description:
Measure:Incidence of transplant related mortality (TRM)
Time Frame:6 months
Safety Issue:
Description:

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • Acute Lymphoblastic Leukemia (ALL)
  • Acute Myelogenous Leukemia (AML)
  • Burkitt's lymphoma
  • Natural killer cell malignancies
  • Chronic myelogenous leukemia
  • Myelodysplastic syndrome
  • Large-cell lymphoma
  • Hodgkin lymphoma
  • Multiple myeloma
  • Chronic lymphocytic leukemia (CLL)
  • Small lymphocytic lymphoma (SLL)
  • Marginal zone B-cell lymphoma
  • Follicular lymphoma
  • Lymphoplasmacytic lymphoma
  • Mantle-cell lymphoma
  • Prolymphocytic leukemia
  • Refractory leukemia
  • MDS
  • Bone marrow failure syndromes
  • Myeloproliferative syndromes

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