Busulfan, Etoposide, Intensity-Modulated Radiation Therapy, and Stem Cell Transplant in Treating Patients With Advanced Myeloid Cancer - Full Text View

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00540995

Purpose

RATIONALE: Giving chemotherapy drugs, such as busulfan and etoposide, and intensity-modulated radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving intensity-modulated radiation therapy together with busulfan and etoposide before a transplant may stop this from happening.

PURPOSE: This phase I/II clinical trial is studying the side effects and best dose of intensity-modulated radiation therapy when given together with busulfan and etoposide followed by a stem cell transplant and to see how well it works in treating patients with advanced myeloid cancer.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Drug: busulfan Drug: etoposide Procedure: allogeneic hematopoietic stem cell transplantation Procedure: bone marrow transplantation Radiation: intensity-modulated radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase I/II Study of Intravenous (IV) Busulfan and Etoposide (VP-16) Combined With Escalated Doses of Large Field Image-Guided Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell Transplantation(HSCT) for Patients With Advanced Myeloid Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Radiation Therapy

Drug Information available for: Busulfan Etoposide Etoposide phosphate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of intensity-modulated radiotherapy (phase I) [ Designated as safety issue: Yes ]
Toxicity (phase I) [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]
Relapse-free survival [ Designated as safety issue: No ]
Event-free survival [ Designated as safety issue: No ]
Transplantation-related mortality [ Designated as safety issue: No ]
Relative risk [ Designated as safety issue: No ]

Secondary Outcome Measures:

Infection [ Designated as safety issue: No ]
Acute graft-versus-host disease [ Designated as safety issue: No ]

Estimated Enrollment:	85
Study Start Date:	October 2006
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To establish the maximum tolerated dose of large field image-guided intensity-modulated radiotherapy (IMRT) using helical tomotherapy when given in combination with busulfan and etoposide as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling in patients with advanced myeloid malignancies. (Phase I)
To describe the toxicities at each dose level studied. (Phase I)
To estimate the radiation doses to the whole body, normal organs, and bone marrow through serial imaging studies following the administration of IMRT. (Phase I)
To estimate the overall survival probability, disease-free survival probability, and relapse rate associated with this preparative regimen. (Phase II)
To characterize the treatment related mortality and toxicity profile (early/late) associated with this regimen. (Phase II)
To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population conditioned with whole-body radiotherapy. (Phase II)

OUTLINE: Patients in the phase I portion of the study are stratified according to age (adult [18-55 years old] vs pediatric [2-17 years old]).

Phase I:
- Preparative regimen: Patients receive busulfan IV on days -15 and -13 and then every 6 hours on days -12 to -8 and etoposide IV on day -3. Patients undergo intensity-modulated radiotherapy (IMRT) via helical tomotherapy on days -9 to -4. Cohorts of patients receive escalating doses of IMRT until the maximum tolerated dose (MTD) is determined
- Hematopoietic stem cell transplantation: Patients undergo allogeneic peripheral stem cell transplantation or bone marrow transplantation on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive best available GVHD prophylaxis excluding methotrexate.
Phase II: Patients undergo treatment as in phase I, receiving IMRT at the MTD.

Eligibility

Ages Eligible for Study:	2 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of one of the following:
- Advanced myeloid malignancy with a disease status of more than second remission, induction failure, or relapse
- Chronic myeloid leukemia in blast crisis
- Myelodysplasia, specifically refractory anemia with excess blasts
HLA (-A, -B, -C, -DR) identical sibling who is willing to donate bone marrow or primed blood stem cells or a 10/10 allele-matched unrelated donor
- All ABO blood group combinations of the donor/recipient are acceptable

PATIENT CHARACTERISTICS:

Inclusion criteria:

Ejection fraction ≥ 50% by MUGA and EKG OR ECHO
Creatinine ≤ 1.2 mg/dL or creatinine clearance > 80 mL/min
Bilirubin ≤ 1.5
AST and ALT < 5 times upper limit of normal
FEV_1 > 50% of normal
DLCO > 50% of normal
Negative pregnancy test

Exclusion criteria:

Pregnant
EKG showing ischemic changes or abnormal rhythm
Abnormal cardiac wall motion

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

Prior etoposide, busulfan, hydroxyurea, and imatinib mesylate allowed
Time from the end of prior induction or reinduction attempt should be ≥ 21 days

Exclusion criteria:

Prior radiotherapy/exposure that would prevent the patient from receiving intensity-modulated radiotherapy (as determined by the radiation oncologist)
Prior blood marrow/marrow transplantation with subsequent relapsed disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00540995

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Anthony S. Stein, MD

Beckman Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	City of Hope Comprehensive Cancer Center ( Anthony S. Stein )
Study ID Numbers:	CDR0000567452, CHNMC-05013
Study First Received:	October 5, 2007
Last Updated:	June 23, 2009
ClinicalTrials.gov Identifier:	NCT00540995 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

refractory anemia with excess blasts
adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
childhood acute myeloid leukemia in remission

recurrent childhood acute myeloid leukemia
childhood myelodysplastic syndromes
blastic phase chronic myelogenous leukemia

Study placed in the following topic categories:

Blast Crisis
Precancerous Conditions
Immunologic Factors
Leukemia, Myeloid, Acute
Etoposide phosphate
Refractory Anemia
Leukemia
Preleukemia
Acute Myelocytic Leukemia
Anemia, Refractory
Acute Myeloid Leukemia, Adult
Alkylating Agents
Etoposide
Hematologic Diseases

Myelodysplastic Syndromes
Myeloproliferative Disorders
Anemia
Leukemia, Myeloid
Immunosuppressive Agents
Recurrence
Acute Myeloid Leukemia, Childhood
Busulfan
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Antineoplastic Agents, Alkylating
Anemia, Refractory, with Excess of Blasts
Chronic Myelogenous Leukemia
Bone Marrow Diseases
Antineoplastic Agents, Phytogenic

Additional relevant MeSH terms:

Precancerous Conditions
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Etoposide phosphate
Leukemia
Preleukemia
Pathologic Processes
Syndrome
Therapeutic Uses
Etoposide
Alkylating Agents

Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Busulfan
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Bone Marrow Diseases
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on August 28, 2009