Study of Gelonin Purging of Autologous Stem Cells for Transplantation - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00043810

Purpose

Patients with Acute Myelogenous Leukemia or Myelodysplastic are able to achieve a complete remission but fail to achieve a prolonged disease-free survival. High dose chemotherapy and autologous bone marrow transplantation has been shown to be effective in this group of patients but hematopoietic recovery is slow, and infectious or bleeding complications are common. The delay in hematopoietic recover is accentuated by the use of purging techniques. This is a novel purging approach for autologous stem cell transplantation in patients with Acute Myelogenous Leukemia or Myelodysplastic syndrome to allow for rapid engraftment with a lower relapse rate therefore improving the therapeutic outcomes

Condition	Intervention	Phase
Acute Myelogenous Leukemia Myelodysplastic Syndrome	Procedure: Gelonin Drug: Busulfan Drug: Fludarabine	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Dose Finding Study of Gelonin Purging of Autologous Stem Cells for Transplantation of Patients With AML/MDS in First or Subsequent Remission

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia Myelodysplastic Syndromes

Drug Information available for: Busulfan Fludarabine Fludarabine monophosphate

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Optimal Dose Gelonin [ Time Frame: 28 days post transplant ] [ Designated as safety issue: Yes ]
Dose-finding success, defined as patient alive and engrafted at day 28 post transplant, represented as number of patient successes with 3 differing doses (5, 10, or 15 nanomolar (nm) gelonin-antiCD33 purged autologous stem cells after a high dose fludarabine/busulfan conditioning regimen).

Enrollment:	3
Study Start Date:	July 2002
Study Completion Date:	March 2005
Primary Completion Date:	March 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Gelonin Purging of ASCT Gelonin Purging of Autologous Stem Cells for Transplantation (ASCT) + Fludara/Busulfan	Procedure: Gelonin Gelonin-AntiCD33 purging, 3 purging concentrations (fixed dose of 5 x 10^6 CD34+ cells/kg to be infused) with 3 dose levels of 1 nanomolar, 5.0 nanomolar and 10.0 nanomolar. Other Name: HuM195-Gelonin conjugate Drug: Busulfan 130 mg/m2 in normal saline over three (3) hours IV every twenty-four (24) hours for four (4) consecutive days (days -6 to -3). Other Names: Busulfex Myleran Drug: Fludarabine 40 mg/m2 in 100 ml of saline over one (1) hour on each of four (4) consecutive days (days - 6 to -3). Other Names: Fludara Fludarabine Phosphate

Arms

Assigned Interventions

Experimental: Gelonin Purging of ASCT

Gelonin Purging of Autologous Stem Cells for Transplantation (ASCT) + Fludara/Busulfan

Procedure: Gelonin

Gelonin-AntiCD33 purging, 3 purging concentrations (fixed dose of 5 x 10^6 CD34+ cells/kg to be infused) with 3 dose levels of 1 nanomolar, 5.0 nanomolar and 10.0 nanomolar.

Other Name: HuM195-Gelonin conjugate

Drug: Busulfan

130 mg/m2 in normal saline over three (3) hours IV every twenty-four (24) hours for four (4) consecutive days (days -6 to -3).

Other Names:

Busulfex
Myleran

Drug: Fludarabine

40 mg/m2 in 100 ml of saline over one (1) hour on each of four (4) consecutive days (days - 6 to -3).

Other Names:

Fludara
Fludarabine Phosphate

Show Detailed Description

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with AML, RAEB-t, RAEB, or CMML who are in first remission and have poor prognosis cytogenetic abnormalities (i.e: deletions of chromosome 5, 7, 20; trisomy 8, t9,22,11q23 abnormalities or complex karyotypes).*
Patients with AML, RAEB-t, RAEB, or CMML who are in second or subsequent remission.
Remission is defined as ANC>1.5 x 109/Lt; Platelet count >100 x 109/Lt, and red cell transfusion independence.
Male or female who have provided written informed consent.
Tumor cells must be > 80 % CD-33 positive by flow cytometry.
For women of childbearing potential (i.e., exclude post-menopausal women, women who have been surgically sterilized), adequate birth control methods must be used. Acceptable birth control methods are limited to oral contraceptives, implants, diaphragm, IUD or spermicide used with a condom)
No chemotherapy for the two weeks prior to entering the study.
No evidence of residual toxic effects from prior chemotherapy.
Patients with proven bacterial infection are not eligible until resolution of the infection (patient afebrile, not on steroids). Patients with active fungal infections are eligible only if evidence of response to antifungal medications is documented and they do not have fever exceeding 38C.
Must have at least 5 x 106 CD34+ peripheral blood stem cells collected.
All patients who have had less than 7 x 106 CD34+ cells/kg collected, should have a bone marrow harvest to serve as back-up.
A minimum of 1 x 106 CD34+ cells/kg of unpurged bone marrow or 2 x 106 CD34+ cells/kg of unpurged peripheral blood need to be stored as backup to be eligible for this protocol.
Patients must have bilirubin less than 2.0, transaminases less than 4 x upper limit of normal.
Pulmonary function tests >50% predicted for DLCO, FVC and FEV1
No active uncontrolled infection
No active CNS disease
No uncontrolled arrythmias
Zubrod Performance Status less than or equal to 2

Exclusion Criteria:

Active CNS disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00043810

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Sergio A. Giralt, MD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Sergio A. Giralt, MD, UT MD Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00043810 History of Changes
Other Study ID Numbers:	ID02-060
Study First Received:	August 14, 2002
Last Updated:	October 21, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

AML
MDS
Gelonin

Purging
Transplant
Peripheral Stem Cell

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Busulfan
Fludarabine monophosphate
Fludarabine
GEL protein, Gelonium multiflorum
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Phytogenic
Protein Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012