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Once Daily Targeted Intravenous (IV) Busulfex as Part of Reduced-toxicity Conditioning for Patients With Refractory Lymphomas Undergoing Allogeneic Transplantation

NCT01203020

Description:

This is a phase II study of allogeneic hematopoietic progenitor cell transplantation (HPCT) followed reduced toxicity conditioning with once daily intravenous Busulfex and fludarabine in patients with relapsed/chemotherapy refractory Hodgkin's and non-Hodgkin's lymphomas.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Once Daily Targeted Intravenous (IV) <span class="go-doc-concept go-doc-intervention">Busulfex</span> as Part of Reduced-toxicity Conditioning for Patients With Refractory Lymphomas Undergoing Allogeneic Transplantation

Title

  • Brief Title: Once Daily Targeted Intravenous (IV) Busulfex as Part of Reduced-toxicity Conditioning for Patients With Refractory Lymphomas Undergoing Allogeneic Transplantation
  • Official Title: Once Daily Intravenous Busulfex as Part of Reduced-toxicity Conditioning for Patients With Relapsed/Refractory Hodgkin's and Non-Hodgkin's Lymphomas Undergoing Allogeneic Hematopoietic Progenitor Cell Transplantation - A Multicenter Phase II Study
  • Clinical Trial IDs

    NCT ID: NCT01203020

    ORG ID: WVU 11310

    Trial Conditions

    Hodgkin's Lymphoma

    Non-Hodgkin's Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    Busulfan Busulfex Allogeneic hematopoietic progenitor cell transplant
    Fludarabine Fludarabine Monophosphate, Fludara Allogeneic hematopoietic progenitor cell transplant

    Trial Purpose

    This is a phase II study of allogeneic hematopoietic progenitor cell transplantation (HPCT)
    followed reduced toxicity conditioning with once daily intravenous Busulfex and fludarabine
    in patients with relapsed/chemotherapy refractory Hodgkin's and non-Hodgkin's lymphomas.

    Detailed Description

    This study hopes to learn if giving intravenous (IV) busulfan with fludarabine before (as a
    conditioning regimen) allogeneic hematopoietic progenitor cell transplantation (HPC) is safe
    and helps patients with NonHodgkins Lymphoma (NHL) and Hodgkins Lymphoma (HL). An HPC
    transplant takes cells from a donors bone marrow and, after chemotherapy treatment with a
    conditioning regimen, infuses the donors cells into the patients body. Busulfan is a
    strong drug that suppresses the immune system and fludarabine is a chemotherapy (cancer
    fighting) drug. These drugs can stop the growth of cancer cells by breaking the
    Deoxyribonucleic acid (DNA) or genetic material which is necessary for the growth of both
    healthy and cancer cells. The use of IV busulfan with fludarabine as a conditioning regimen
    prior to HPC transplant is investigational (not approved by the Food and Drug Administration
    [FDA]).

    Busulfan is only given once daily by IV in this study, which is also not approved by the
    FDA. Patients in this study will go through standard procedures for their disease like
    medical history, physical exam, blood tests, Multi Gated Acquisition Scan (MUGA) scan or
    echocardiogram, bone marrow aspirate or biopsy, and lung functions test. Patients will be
    asked to donate additional blood and bone marrow for this study and for potential future
    research on their blood related to this study. Because of the normal procedures for HPC
    transplants patients in this study will be hospitalized for 4 to 6 weeks or longer and will
    make frequent trips to the clinic to visit the study doctor for supervision for at least one
    year. Each patient will also have to have a central venous catheter inserted into a large
    vein above the heart. This is used to give the drugs and to take blood samples.

    Participation in this study will last about two years. The study expects to enroll 32
    patients and will open to at least two collaborating institutions in the future. Upon
    initial Institutional Review Board (IRB) approval enrollment will only occur at West
    Virginia University (WVU). The IRB will be notified before enrollment occurs at other
    institutions.

    Trial Arms

    Name Type Description Interventions
    Allogeneic hematopoietic progenitor cell transplant Experimental Intravenous busulfex 130mg/m2 on days -6 to -3 before transplant Busulfan, Fludarabine

    Eligibility Criteria

    Inclusion Criteria:

    1. Patients aged 18-70 years of age are eligible.

    2. Eligible histologies include:

    - B-cell, T-cell or NK-cell NHL refractory to frontline or salvage therapy defined
    as failure to achieve complete or partial remission according to standard
    criteria.

    - Diffuse large B-cell lymphoma relapsing within 12 months of finishing a
    rituximab containing first line chemotherapy regimen (regardless of response to
    salvage chemotherapy)or with evidence of c-myc. Primary refractory NHL
    (regardless of response to salvage chemotherapy).

    - Hodgkin lymphoma which is chemorefractory after at least two prior therapies.

    - Hodgkin and NHL in an untreated relapse.

    - Transformed NHL or chronic lymphocytic leukemia undergoing Richter's
    transformation (regardless of response to last chemotherapy). Patients with
    chemosensitive relapsed NHLs or Hodgkin lymphoma, but considered ineligible for
    curative therapy with autologous transplantation, because of (a) inability to
    collect stem cells, (b) prior autografting, (c) presence of myelodysplasia or
    (d) histology not considered curable with autografting in opinion of treating
    physician will be eligible.

    3. All patients must have at least one suitable HLA-matched sibling or volunteer
    unrelated donor available (according to institutional guidelines). HLA typing should
    be performed at least at serological level for HLA-A, -B, and -C and at allele level
    for HLA-DRB1. One antigen or allele level mismatch will be permitted between the
    donor and the recipient; however each donor/recipient pair must match at HLA-DRB1 at
    allele level.

    4. Patient must be able to provide informed consent.

    5. Left ventricular ejection fraction 40%. No uncontrolled arrhythmias or uncontrolled
    New York Heart Association class III-IV heart failure.

    6. Bilirubin, aspartate aminotransferase (AST), and Alanine transaminase (ALT) 3 x
    normal; and absence of hepatic cirrhosis.

    7. Adequate renal function as defined by a serum creatinine clearance of 40% of normal
    calculated by Cockcroft-Gault equation.

    8. DLCO (diffusion capacity; corrected for hemoglobin) or forced expiratory volume
    (FEV1) 50% of predicted.

    9. Karnofsky performance status 70.

    10. A negative pregnancy test will be required for all women of child bearing potential.
    Breast feeding is not permitted.

    Exclusion Criteria:

    1. Patients eligible for potentially curative therapy with autologous transplantation.

    2. Patients with lymphoblastic lymphoma.

    3. Patients with positive human immunodeficiency virus (HIV) serology.

    4. Clinical evidence of uncontrolled bacterial, viral or fungal infection at the time of
    transplant conditioning.

    5. Prior allogeneic transplantation.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 70 Years

    Eligible Gender: Both

    Primary Outcome Measures

    To assess 1-year progression free survival (PFS) of patients with chemotherapy refractory Hodgkin's and non-Hodgkin's lymphoma (NHL) undergoing reduced-toxicity conditioning (RTC) with once daily intravenous Busulfex and fludarabine.

    Secondary Outcome Measures

    To record 1 and 2 year overall survival (OS) following transplantation.

    To record 2 year PFS.

    To assess nonrelapse mortality (NRM) following RTC transplantation at day +100 and 1-year.

    To assess relapse rate following transplantation at day +100 and 1-year.

    To assess disease response rate (RR) following transplantation at day +100 and at 1-year.

    To correlate OS, PFS, RR, NRM following HPCT with systemic busulfan exposure.

    To assess rates of acute and chronic graft versus host disease (GVHD).

    Time to successful neutrophil engraftment.

    Time to successful platelet engraftment.

    To assess rates of primary and secondary graft failure.

    To assess rates of primary and secondary graft rejection.

    To assess rates of pulmonary toxicity and venous occlusive disease (VOD) post transplantation, and assess correlation with Busulfex exposure levels.

    To assess lineage specific chimerism kinetics of donor cells following once daily IV Busulfex based RTC at days +30, +100, +180 and +365.

    To correlate chimerism kinetics following transplantation with Busulfex exposure levels.

    To determine immune reconstitution pattern at days +30, +100, +180, and +365.

    To evaluate biologic & genetic markers associated with the malignancy, GVHD and/or the treatment.

    Trial Keywords

    Hodgkin's

    non-Hodgkin's

    lymphomas

    allogeneic hematopoietic progenitor cell transplant

    HPCT

    busulfex

    fludarabine

    reduced-toxicity conditioning

    reduced-intensity conditioning