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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02145039
Recruitment Status : Terminated (Replaced by another study.)
First Posted : May 22, 2014
Results First Posted : December 26, 2019
Last Update Posted : December 26, 2019
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Leukemias Burkitt's Lymphoma Chronic Myelogenous Leukemia Drug: Fludarabine Drug: Cyclophosphamide Radiation: Total Body Irradiation Biological: Haploidentical stem cell transplant Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduced Intensity Conditioning (RIC) and Transplantation of HLA(Human Leukocyte Antigen)-Haploidentical Related Bone Marrow (Haplo-BM) For Patients With Hematologic Diseases
Actual Study Start Date : October 2014
Actual Primary Completion Date : January 2018
Actual Study Completion Date : January 2019

Arm Intervention/treatment
Experimental: Haploidentical stem cell transplant
This 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).
Drug: Fludarabine
Fludarabine 30 mg/m2 IV over 30-60 minutes on days -6 through -2 before transplant.
Other Name: Fludara

Drug: Cyclophosphamide
Cyclophosphamide 14.5 mg/kg IV over 1-2 hours on days -6 and -5 before transplant and Cyclophosphamide 50 mg/kg IV on days 3 and 4 post-transplant.

Radiation: Total Body Irradiation
TBI 200cGy on day -1 before transplant.
Other Name: TBI

Biological: Haploidentical stem cell transplant
Non-T-cell depleted bone marrow infusion
Other Name: HSCT

Primary Outcome Measures :
  1. 2 Year Survival [ Time Frame: 2 years ]
    Percentage of patients that survive 2 years post-transplant

Secondary Outcome Measures :
  1. Number of Patients With Hematopoietic Engraftment [ Time Frame: 42 days ]
    Engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10^8/L for 3 consecutive measurements.

  2. Number of Patients With Chimerism [ Time Frame: 100 days ]
    Number of patients with chimerism at day 100, 6 months and 1 year

  3. Number of Patients Experiencing Acute Graft-versus-host Disease by 100 Days [ Time Frame: 100 days ]
  4. Number of Patients Experiencing Chronic Graft-versus-host Disease by 1 Year [ Time Frame: 1 year ]
  5. Number of Patients Experiencing Transplant Related Mortality (TRM) [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 74 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 multigated acquisition scan (MUGA) and echocardiography, such should be clearly stated in the physician's note
    • Pulmonary: Diffusing capacity of lung for carbon monoxide (DLCO) > 30% predicted, and absence of O2 requirements. For children that are not able to cooperate with pulmonary function tests (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 bone marrow transplant (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.
  • Chronic myeloid leukemia (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02145039

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United States, Minnesota
University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
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Principal Investigator: Claudio Brunstein, MD University of Minnesota
  Study Documents (Full-Text)

Documents provided by Masonic Cancer Center, University of Minnesota:
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Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT02145039    
Other Study ID Numbers: 2013OC116
MT2013-33C ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
First Posted: May 22, 2014    Key Record Dates
Results First Posted: December 26, 2019
Last Update Posted: December 26, 2019
Last Verified: December 2019
Keywords provided by Masonic Cancer Center, University of Minnesota:
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
Myelodysplastic syndrome (MDS)
Bone marrow failure syndromes
Myeloproliferative syndromes
Additional relevant MeSH terms:
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Burkitt Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hematologic Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents