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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by West Virginia University
Sponsor:
Information provided by (Responsible Party):
Dr. Abraham Kanate, West Virginia University
ClinicalTrials.gov Identifier:
NCT01203020
First received: September 13, 2010
Last updated: January 3, 2014
Last verified: January 2014

September 13, 2010
January 3, 2014
September 2010
December 2014   (final data collection date for primary outcome 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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01203020 on ClinicalTrials.gov Archive Site
  • To record 1 and 2 year overall survival (OS) following transplantation. [ Time Frame: At 1 year and 2 years ] [ Designated as safety issue: No ]
  • To record 2 year PFS. [ Time Frame: 12/31/13 ] [ Designated as safety issue: No ]
  • To assess nonrelapse mortality (NRM) following RTC transplantation at day +100 and 1-year. [ Time Frame: 12/31/13 ] [ Designated as safety issue: Yes ]
  • To assess relapse rate following transplantation at day +100 and 1-year. [ Time Frame: 12/31/13 ] [ Designated as safety issue: No ]
  • To assess disease response rate (RR) following transplantation at day +100 and at 1-year. [ Time Frame: 12/31/13 ] [ Designated as safety issue: No ]
  • To correlate OS, PFS, RR, NRM following HPCT with systemic busulfan exposure. [ Time Frame: 12/31/13 ] [ Designated as safety issue: Yes ]
  • To assess rates of acute and chronic graft versus host disease (GVHD). [ Time Frame: 12/31/13 ] [ Designated as safety issue: Yes ]
  • Time to successful neutrophil engraftment. [ Time Frame: 12/31/13 ] [ Designated as safety issue: Yes ]
  • Time to successful platelet engraftment. [ Time Frame: 12/31/13 ] [ Designated as safety issue: Yes ]
  • To assess rates of primary and secondary graft failure. [ Time Frame: 12/31/13 ] [ Designated as safety issue: Yes ]
  • To assess rates of primary and secondary graft rejection. [ Time Frame: 12/31/13 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • To assess lineage specific chimerism kinetics of donor cells following once daily IV Busulfex based RTC at days +30, +100, +180 and +365. [ Time Frame: 12/31/13 ] [ Designated as safety issue: No ]
  • To correlate chimerism kinetics following transplantation with Busulfex exposure levels. [ Time Frame: 12/31/13 ] [ Designated as safety issue: No ]
  • To determine immune reconstitution pattern at days +30, +100, +180, and +365. [ Time Frame: 12/31/13 ] [ Designated as safety issue: No ]
  • To evaluate biologic & genetic markers associated with the malignancy, GVHD and/or the treatment. [ Time Frame: 12/31/13 ] [ Designated as safety issue: No ]
  • To record 1 and 2 year overall survival (OS) following transplantation. [ Designated as safety issue: No ]
  • To record 2 year PFS. [ Designated as safety issue: No ]
  • To assess nonrelapse mortality (NRM) following RTC transplantation at day +100 and 1-year. [ Designated as safety issue: Yes ]
  • To assess relapse rate following transplantation at day +100 and 1-year. [ Designated as safety issue: No ]
  • To assess disease response rate (RR) following transplantation at day +100 and at 1-year. [ Designated as safety issue: No ]
  • To correlate OS, PFS, RR, NRM following HSCT with systemic busulfan exposure. [ Designated as safety issue: Yes ]
  • To assess rates of acute and chronic graft versus host disease (GVHD). [ Designated as safety issue: Yes ]
  • Time to successful neutrophil engraftment. [ Designated as safety issue: Yes ]
  • Time to successful platelet engraftment. [ Designated as safety issue: Yes ]
  • To assess rates of primary and secondary graft failure. [ Designated as safety issue: Yes ]
  • To assess rates of primary and secondary graft rejection. [ Designated as safety issue: Yes ]
  • To assess rates of pulmonary toxicity and venous occlusive disease (VOD) post transplantation, and assess correlation with Busulfex exposure levels. [ Designated as safety issue: Yes ]
  • To assess lineage specific chimerism kinetics of donor cells following once daily IV Busulfex based RTC at days +30, +100, +180 and +365. [ Designated as safety issue: No ]
  • To correlate chimerism kinetics following transplantation with Busulfex exposure levels. [ Designated as safety issue: No ]
  • To determine immune reconstitution pattern at days +30, +100, +180, and +365. [ Designated as safety issue: No ]
  • To evaluate biologic & genetic markers associated with the malignancy, GVHD and/or the treatment. [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Once Daily Targeted Intravenous (IV) Busulfex as Part of Reduced-toxicity Conditioning for Patients With Refractory Lymphomas Undergoing Allogeneic Transplantation
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma
  • Drug: Busulfan
    Busulfex 130 mg/m2 intravenous piggy back (IVPB) for 4 days (Day -6 to -3) pharmacokinetic (PK) samples for Busulfex dose adjustment drawn on Day -6
    Other Name: Busulfex
  • Drug: Fludarabine
    Fludarabine 40 mg/m2 IVPB for 4 days (Day -6 to -3)
    Other Names:
    • Fludarabine Monophosphate
    • Fludara
Experimental: Allogeneic hematopoietic progenitor cell transplant
Intravenous busulfex 130mg/m2 on days -6 to -3 before transplant
Interventions:
  • Drug: Busulfan
  • Drug: Fludarabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
32
December 2016
December 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 70 Years
No
Contact: Pam Bunner, MT, CCRC 304-598-4511 bunnerp@wvuhealthcare.com
Contact: Crystal Stevens, MT 304-598-4512 stevensc@wvuhealthcare.com
United States
 
NCT01203020
WVU 11310
Yes
Dr. Abraham Kanate, West Virginia University
Dr. Abraham Kanate
Not Provided
Principal Investigator: Abraham Kanate, MD West Virginia University
West Virginia University
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP