Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)

NCT00361140 | Completed Phase 4 Results DMC

• 1 other identifier: MCC-14178
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Pre-transplant conditioning will include Fludarabine and dose-escalated Busulfan on days -6, -5, -4, and -3. Daily treatment doses will be adjusted to achieve target area under the plasma concentration time curve (AUC). Day 0 is the day of hematopoietic progenitor cell reinfusion. Supportive care will be based on institutional guidelines. Blood samples will be collected for dose modification based on the AUC levels. Dose escalation will proceed to determine the maximally tolerated level or AUC to evaluate the potential therapeutic benefit of higher doses of busulfan.

Conditions

Myelodysplastic Syndromes; Myeloproliferative Disorders; Leukemia, Lymphocytic; Myeloma; Lymphoma

Keywords

Busulfan; Fludarabine; Chimerism; Allogeneic stem cell transplantation (HCT); Myelodysplastic Syndromes; Leukemia Myeloproliferative disorders (MPD); Leukemia, Lymphocytic; Myeloma; Lymphoma; AUC; Hematologic malignancies

Outcome Measures

Primary Outcomes (1)

• Non-relapse Mortality

  The number of participants dead due to causes unrelated to relapse within the first 100 days post transplant.

  100 days

Secondary Outcomes (1)

• Severe Venous Occlusive Disease (VOD)/ Sinusoidal Obstructive Syndrome (SOS)

  100 days

Study Arms (3)

AUC 6000

EXPERIMENTAL

Busulfan AUC Level 1: 6000 +/- 600 uM-min Fludarabine 40mg/m2 IV over 1 hour

Drug: Busulfan; Drug: Fludarabine

AUC 7500

EXPERIMENTAL

Busulfan AUC Level 2: 7500 +/- 750 uM-min Fludarabine 40mg/m2 IV over 1 hour

Drug: Busulfan; Drug: Fludarabine

AUC 9000

EXPERIMENTAL

AUC Level 3: 9000 +/- 900 uM-min Fludarabine 40mg/m2 IV over 1 hour

Drug: Busulfan; Drug: Fludarabine

Interventions

Busulfan DRUG

Bu IV (BusulfexR) over 3 hours on days -6, -5, -4, and -3. Day -6 and -5 doses for patients on Level 1 will be 170mg/m2. This dose is based on the dose used by DeLima (2004) adjusted proportionately to achieve an AUC of 6000uM-min. Subsequent daily doses for patients on Level 1 will be adjusted to achieve an average AUC of 6000uM-min. Day -6 and -5 doses for patients on Level 2 will be based on the mean dose required on Level 1 to achieve target AUC then adjusted proportionally for new target AUC. Subsequent daily doses will be adjusted to achieve target AUCs.

Also known as: Busulfex(R)

AUC 6000; AUC 7500; AUC 9000

Fludarabine DRUG

Fludarabine 40mg/m2 IV over 1 hour on days -6, -5, -4, and -3

Also known as: Fludarabine Phosphate

AUC 6000; AUC 7500; AUC 9000

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HLA A, B, C, DRB1 8/8 or 7/8 matched related or unrelated donor. HLA-DQ mismatches are not considered ie they are allowed in addition to these.
• Histologically confirmed diagnosis by pathologic review
• Diagnosis of any of the following:
• Acute myelogenous leukemia (AML), Acute lymphoblastic leukemia (ALL), or Non-Hodgkin's Leukemia (NHL), in first remission with high risk of relapse, refractory to primary chemotherapy, or after first relapse; acute biphenotypic or undifferentiated leukemia is also included
• Myelodysplastic Syndrome (MDS), with IPSS \>1
• Chronic myelogenous leukemia (CML), with GleevecR-refractory or intolerant chronic phase, or beyond chronic phase by morphology or cytogenetics
• Myeloproliferative disorders, including Ph-negative CML, myelofibrosis and chronic myelomonocytic leukemia (CMML)
• Multiple myeloma, refractory to two or more lines of therapy.
• Chronic lymphocytic leukemia (CLL), refractory to fludarabine
• Hodgkin's disease, refractory to primary chemotherapy or after first relapse
• Karnofsky performance status 70-100%
• Organ function:
• Pulmonary: Diffusing capacity of lung for carbon monoxide (DLCO) greater than 50%
• Cardiac: Left ventricular ejection fraction greater than 45%
• Renal: Creatinine clearance (measured or calculated) equal or greater than 50 ml/min

You may not qualify if:

• Pregnant or lactating women
• HIV or seropositive, confirmed by nucleic acid test (NAT)
• Active central nervous system (CNS) malignancy
• Patients with current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings) are ineligible.
• Unfavorable psychosocial evaluation or history of poor compliance to prescribed medical care
• Current use of metronidazole or acetominophen, unless medically necessary; patients must discontinue use of these agents at least 7 days prior to the start of BusulfexR administration
• Prior use of MylotargR (gemtuzumab ozogamicin)
• Prior Hematopoietic Cell Transplantation (HCT)
• Prior chest or abdominal irradiation with greater than 1800 cGy
• Presence of any of the following comorbid conditions:
• History of myocardial infarction or coronary artery disease requiring catheterization or stent placements less than six months prior to enrollment. All participants with history of myocardial infarction or coronary artery disease must have clearance by a cardiologist to be enrolled.
• Congestive heart failure (even if symptomatically controlled)
• Peripheral vascular disease (including intermittent claudication or history of bypass for arterial insufficiency)
• Untreated thoracic or abdominal aneurysm (6 cm or more)
• History of any cerebrovascular accident including transient ischemic attacks

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Perkins JB, Kim J, Anasetti C, Fernandez HF, Perez LE, Ayala E, Kharfan-Dabaja MA, Tomblyn MR, Sullivan DM, Pidala JA, Field TL. Maximally tolerated busulfan systemic exposure in combination with fludarabine as conditioning before allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012 Jul;18(7):1099-107. doi: 10.1016/j.bbmt.2011.12.584. Epub 2011 Dec 23.

  PMID: 22198540 RESULT

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Myelodysplastic Syndromes; Myeloproliferative Disorders; Leukemia, Lymphoid; Neoplasms, Plasma Cell; Lymphoma; Hematologic Neoplasms

Interventions

Busulfan; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

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: Dr. Teresa Field
• Organization: Moffitt Cancer Center

Teresa.Field@moffitt.org

(813) 745-7202

Study Officials

• Teresa Field, PhD, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• Janelle Perkins, PharmD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2006
• First Posted: August 7, 2006
• Study Start: August 1, 2005
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: March 3, 2017
• Results First Posted: June 27, 2013

Record last verified: 2013-06

Locations

US (1)