Clinical Trials /

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

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

  • ORG STUDY ID: WVU 11310
  • NCT ID: NCT01203020

Conditions

  • Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
BusulfanBusulfexAllogeneic hematopoietic progenitor cell transplant
FludarabineFludarabine Monophosphate, FludaraAllogeneic hematopoietic progenitor cell transplant

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 Non-Hodgkin´s Lymphoma (NHL) and Hodgkin´s Lymphoma (HL). An HPC
      transplant takes cells from a donor´s bone marrow and, after chemotherapy treatment with a
      conditioning regimen, infuses the donor´s cells into the patient´s 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

NameTypeDescriptionInterventions
Allogeneic hematopoietic progenitor cell transplantExperimentalIntravenous 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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Time Frame:1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To record 1 and 2 year overall survival (OS) following transplantation.
Time Frame:At 1 year and 2 years
Safety Issue:
Description:
Measure:To record 2 year PFS.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:To assess nonrelapse mortality (NRM) following RTC transplantation at day +100 and 1-year.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:To assess relapse rate following transplantation at day +100 and 1-year.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:To assess disease response rate (RR) following transplantation at day +100 and at 1-year.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:To correlate OS, PFS, RR, NRM following HPCT with systemic busulfan exposure.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:To assess rates of acute and chronic graft versus host disease (GVHD).
Time Frame:12/31/13
Safety Issue:
Description:
Measure:Time to successful neutrophil engraftment.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:Time to successful platelet engraftment.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:To assess rates of primary and secondary graft failure.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:To assess rates of pulmonary toxicity and venous occlusive disease (VOD) post transplantation, and assess correlation with Busulfex exposure levels.
Time Frame:12/31/13
Safety Issue:
Description:
Measure:To correlate chimerism kinetics following transplantation with Busulfex exposure levels.
Time Frame:12/31/13
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:West Virginia University

Trial Keywords

  • Hodgkin's
  • non-Hodgkin's
  • lymphomas
  • allogeneic hematopoietic progenitor cell transplant
  • HPCT
  • busulfex
  • fludarabine
  • reduced-toxicity conditioning
  • reduced-intensity conditioning

Last Updated

April 7, 2021