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

NCT01203020 | Completed Phase 2 Results DMC

• 1 other identifier: WVU 11310
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Percentage of 1 Year Overall Survival (OS)

  Percentage of participants--1 year overall survival (OS) following transplantation.

  1 year

• Percentage of 2 Year Overall Survival (OS)

  Percentage of participants-- 2 Year Overall Survival (OS) post transplant

  At 2nd year

• Percentage of 1-year Progression Free Survival (PFS)

  Percentage of 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.

  At 1 year

• Percentage of 2-year Progression Free Survival (PFS)

  Percentage of 2-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.

  At 2 year

Secondary Outcomes (5)

• Relapse Rate (RR) Following Transplantation at 1-year.

  At 1 year

• Relapse Rate (RR) Following Transplantation at 2-year.

  At 2 year

• Non-Relapse Mortality (NRM) Following RTC Transplantation at 1 Year.

  At 1 year

• Non-Relapse Mortality (NRM) Following RTC Transplantation at 2 Years.

  At 2 years

• Rates of Acute and Chronic Graft Versus Host Disease (GVHD).

  Day 100

Study Arms (1)

Allogeneic hematopoietic progenitor cell transplant

EXPERIMENTAL

Intravenous busulfex 130mg/m2 on days -6 to -3 before transplant

Drug: Busulfan; Drug: Fludarabine

Interventions

Busulfan DRUG

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

Also known as: Busulfex

Allogeneic hematopoietic progenitor cell transplant

Fludarabine DRUG

Fludarabine 40 mg/m2 IVPB for 4 days (Day -6 to -3)

Also known as: Fludarabine Monophosphate, Fludara

Allogeneic hematopoietic progenitor cell transplant

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-70 years of age are eligible.
• 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.
• 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.
• Patient must be able to provide informed consent.
• Left ventricular ejection fraction ≥ 40%. No uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure.
• Bilirubin, aspartate aminotransferase (AST), and Alanine transaminase (ALT) ≤ 3 x normal; and absence of hepatic cirrhosis.
• Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
• DLCO (diffusion capacity; corrected for hemoglobin) or forced expiratory volume (FEV1) ≥ 50% of predicted.
• Karnofsky performance status ≥ 70.
• A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.

You may not qualify if:

• Patients eligible for potentially curative therapy with autologous transplantation.
• Patients with lymphoblastic lymphoma.
• Patients with positive human immunodeficiency virus (HIV) serology.
• Clinical evidence of uncontrolled bacterial, viral or fungal infection at the time of transplant conditioning.
• Prior allogeneic transplantation.

Sponsors & Collaborators

• West Virginia University: lead

Study Sites (1)

West Virginia University Hospitals Mary Babb Randolph Cancer Center

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Lymphoma

Interventions

Busulfan; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Abraham Kanate
• Organization: WV Cancer Institute

tlr0011@hsc.wvu.edu

3049065228

Study Officials

• Abraham Kanate, MD

  West Virginia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2010
• First Posted: September 16, 2010
• Study Start: October 12, 2010
• Primary Completion: September 27, 2021
• Study Completion: September 27, 2021
• Last Updated: July 13, 2023
• Results First Posted: July 13, 2023

Record last verified: 2023-06

Locations

US (1)