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

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: NCT01203020
Recruitment Status : Active, not recruiting
First Posted : September 16, 2010
Last Update Posted : April 8, 2021
Information provided by (Responsible Party):
West Virginia University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hodgkin's Lymphoma Non-Hodgkin's Lymphoma Drug: Busulfan Drug: Fludarabine Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 12, 2010
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Allogeneic hematopoietic progenitor cell transplant
Intravenous busulfex 130mg/m2 on days -6 to -3 before transplant
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. To record 1 and 2 year overall survival (OS) following transplantation. [ Time Frame: At 1 year and 2 years ]
  2. To record 2 year PFS. [ Time Frame: 12/31/13 ]
  3. To assess nonrelapse mortality (NRM) following RTC transplantation at day +100 and 1-year. [ Time Frame: 12/31/13 ]
  4. To assess relapse rate following transplantation at day +100 and 1-year. [ Time Frame: 12/31/13 ]
  5. To assess disease response rate (RR) following transplantation at day +100 and at 1-year. [ Time Frame: 12/31/13 ]
  6. To correlate OS, PFS, RR, NRM following HPCT with systemic busulfan exposure. [ Time Frame: 12/31/13 ]
  7. To assess rates of acute and chronic graft versus host disease (GVHD). [ Time Frame: 12/31/13 ]
  8. Time to successful neutrophil engraftment. [ Time Frame: 12/31/13 ]
  9. Time to successful platelet engraftment. [ Time Frame: 12/31/13 ]
  10. To assess rates of primary and secondary graft failure. [ Time Frame: 12/31/13 ]
  11. 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 ]
  12. To correlate chimerism kinetics following transplantation with Busulfex exposure levels. [ Time Frame: 12/31/13 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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): NCT01203020

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United States, West Virginia
West Virginia University Hospitals Mary Babb Randolph Cancer Center
Morgantown, West Virginia, United States, 26506
Sponsors and Collaborators
West Virginia University
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Principal Investigator: Abraham Kanate, MD West Virginia University
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Responsible Party: West Virginia University Identifier: NCT01203020    
Other Study ID Numbers: WVU 11310
First Posted: September 16, 2010    Key Record Dates
Last Update Posted: April 8, 2021
Last Verified: April 2021
Keywords provided by West Virginia University:
allogeneic hematopoietic progenitor cell transplant
reduced-toxicity conditioning
reduced-intensity conditioning
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists