Busulfan-fludarabine Conditioning and T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With Advanced Hematologic Malignancies

NCT00943319 | Completed Phase 1 Results DMC

• 1 other identifier: 12-0132
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is:

1. 1.To establish the maximally tolerated dose (MTD) of intravenous busulfan (Busulfan®) in combination with fludarabine as conditioning regimen for transplantation with in-vivo T-cell depletion.
2. 2.To evaluate disease free and overall survival after this conditioning regimen in patients with advanced acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
3. 3.To evaluate potential pharmacogenomic determinants of toxicity of this regimen.
4. 4.To evaluate potential pharmacogenomic determinants of efficacy of this regimen.

Conditions

Leukemia; Lymphoma; Myeloma

Keywords

Cancers of the blood

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Maximally tolerated area under the curve of intravenous busulfan (Busulfan®) in combination with fludarabine as conditioning regimen for transplantation with in-vivo T-cell depletion. The number reported will be an Area Under the Curve (AUC) measure reported in µmol-min/L.

  5 years

Secondary Outcomes (2)

• Overall Survival

  5 years

• Disease Free Survival

  5 years

Study Arms (1)

Busulfan and fludarabine

EXPERIMENTAL

Intravenous busulfan (Busulfan®) in combination with fludarabine

Drug: Busulfan; Drug: Fludarabine; Drug: Campath; Procedure: Stem Cell Transplant

Interventions

Busulfan DRUG

Daily intravenous dosing to target AVC

Busulfan and fludarabine

Fludarabine DRUG

Fludarabine dosing will be based on actual body weight. Fludarabine will be infused over 30 minutes before busulfan treatment dose.

Busulfan and fludarabine

Campath DRUG

All patients will receive premedication for Campath (daily doses of 20 mg are repeated for up to five times).

Busulfan and fludarabine

Stem Cell Transplant PROCEDURE

Infusion of bone marrow and donors(related/ unrelated).

Busulfan and fludarabine

Eligibility Criteria

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

You may qualify if:

• Phase I portion:
• Relapsed or refractory acute myelogenous or lymphoid leukemia.
• Chronic myelogenous leukemia in accelerated phase or blast-crisis.
• Recurrent or refractory malignant lymphoma or Hodgkin's disease
• Recurrent or refractory multiple myeloma.
• Chronic lymphocytic leukemia, relapsed or with poor prognostic features.
• Myeloproliferative disorder (polycythemia vera, myelofibrosis) with transformation
• Myelodysplastic syndromes with more than 5% blasts.
• Phase II portion:
• AML with active disease or beyond CR2.
• MDS with more than 5% blasts.

You may not qualify if:

• Clinical progression. Such patients may be treated on other treatment protocols or at the investigator's discretion. Such patients will continue to be monitored for survival and, may be asked to continue to provide specimens for studies of minimal residual disease and immune reconstitution as other treatments are recommended.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• O'Donnell PH, Artz AS, Undevia SD, Pai RK, Del Cerro P, Horowitz S, Godley LA, Hart J, Innocenti F, Larson RA, Odenike OM, Stock W, Van Besien K. Phase I study of dose-escalated busulfan with fludarabine and alemtuzumab as conditioning for allogeneic hematopoietic stem cell transplant: reduced clearance at high doses and occurrence of late sinusoidal obstruction syndrome/veno-occlusive disease. Leuk Lymphoma. 2010 Dec;51(12):2240-9. doi: 10.3109/10428194.2010.520773. Epub 2010 Oct 4.

  PMID: 20919852 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma; Neoplasms, Plasma Cell

Interventions

Busulfan; fludarabine; Alemtuzumab; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Andrew Artz
• Organization: UChicago

aartz@medicine.bsd.uchicago.edu

773-834-8980

Study Officials

• Andrew Artz, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2009
• First Posted: July 22, 2009
• Study Start: March 1, 2012
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2018
• Last Updated: February 4, 2019
• Results First Posted: February 4, 2019

Record last verified: 2019-02

Locations

US (1)