Low-Dose Total-Body Irradiation, Fludarabine, and Alemtuzumab Followed By Allogeneic Stem Cell Transplant in Treating Patients With Myeloproliferative Disorder, Myelodysplastic Syndrome, Acute Myeloid Leukemia, or Chronic Myelogenous Leukemia - Full Text View

Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and total-body irradiation before a donor stem cell transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect).Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, before transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving low-dose total-body irradiation together with fludarabine and alemtuzumab followed by a donor stem cell transplant works in treating patients with myeloproliferative disorder, myelodysplastic syndrome, acute myeloid leukemia, or chronic myelogenous leukemia.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders Leukemia Myelodysplastic Syndromes	Drug: alemtuzumab Drug: fludarabine phosphate Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Procedure: radiation therapy	Phase II

MedlinePlus related topics:

Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

ChemIDplus related topics:

Fludarabine Fludarabine monophosphate Alemtuzumab Campath

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label

Official Title:	Safety And Efficacy of Sub-Myeloablative Allogeneic Stem Cell Transplantation For Patients With Myeloproliferative Disorder (MPD), Myelodysplastic Syndrome (MDS), Acute Myelogenous Leukemia (AML) or Chronic Myelogenous Leukemia

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

Primary Outcome Measures:

Nonrelapse mortality at 100 days [ Designated as safety issue: No ]
Graft-vs-host disease (GVHD) at 100 days [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]
Survival [ Designated as safety issue: No ]
Relapse [ Designated as safety issue: No ]
Complete remission [ Designated as safety issue: No ]
Acute and chronic GVHD [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Hematopoietic engraftment [ Designated as safety issue: No ]

Estimated Enrollment:	44
Study Start Date:	December 2001
Estimated Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the safety and feasibility of a submyeloablative conditioning regimen comprising low-dose total body irradiation, fludarabine, and alemtuzumab in patients receiving allogeneic stem cell infusion for myeloproliferative disorders, myelodysplastic syndromes, acute myeloid leukemia or chronic myelogenous leukemia as defined by non-relapse mortality and graft rejection at day 100 after transplantation.

Secondary

Determine complete remission at day 100 in patients treated with this regimen.
Determine 1-year disease-free survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Conditioning: Patients undergo low-dose total body irradiation on day -6. Patients receive fludarabine IV over 30 minutes and alemtuzumab IV over 2 hours on days -5 to -2.
Transplantation: Allogeneic stem cells are infused on day 0. Patients are followed monthly for 1 year, then every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 69 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Myelodysplastic syndromes with International Prognostic Scoring System score greater than 0
- One of the following myeloproliferative disorders:
  - Primary myelofibrosis with Lile score of 1 or 2
  - Polycythemia vera (PV) or essential thrombocythemia transformed to acute myeloid leukemia or myelofibrosis and PV "spent phase"
- Acute myeloid leukemia
- Chronic myelogenous leukemia
Available 5/6 or 6/6 related or unrelated (molecular typing for DRB1) healthy donor
No active CNS disease from hematologic disorder

PATIENT CHARACTERISTICS:

Age

Under 70

Performance status

Zubrod 0-2

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

No active hepatitis
No cirrhosis
Bilirubin no greater than 3 times normal
SGOT and SGPT no greater than 3 times normal

Renal

No dependence on hemodialysis

Cardiovascular

No unstable angina
No uncompensated congestive heart failure
No unstable cerebral vascular disease
No hemorrhagic stroke within the past 6 months

Pulmonary

No severe chronic pulmonary disease requiring oxygen

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
HIV negative
No concurrent uncontrolled infection
No concurrent solid organ malignancy not in remission, except stage 0 or A prostate cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00069992

Locations


United States, Texas
	Dan L. Duncan Cancer Center at Baylor College of Medicine
	Houston, Texas, United States, 77030
	Methodist Hospital
	Houston, Texas, United States, 77030
	Texas Children's Hospital
	Houston, Texas, United States, 77030

Sponsors and Collaborators

Baylor College of Medicine

Investigators


Study Chair:	George Carrum, MD	Baylor College of Medicine

More Information

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

Study ID Numbers:	CDR0000328132, BCM-H-10857
First Received:	October 3, 2003
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00069992
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

polycythemia vera

essential thrombocythemia

de novo myelodysplastic syndromes

previously treated myelodysplastic syndromes

secondary myelodysplastic syndromes

chronic idiopathic myelofibrosis

chronic myelogenous leukemia

adult acute myeloid leukemia with 11q23 (MLL) abnormalities

adult acute myeloid leukemia with inv(16)(p13;q22)

adult acute myeloid leukemia with t(15;17)(q22;q12)

adult acute myeloid leukemia with t(16;16)(p13;q22)

adult acute myeloid leukemia with t(8;21)(q22;q22)

childhood myelodysplastic syndromes

Study placed in the following topic categories:

Polycythemia

Precancerous Conditions

Chronic myelogenous leukemia

Leukemia, Myeloid, Acute

Leukemia

Preleukemia

Alemtuzumab

Hemorrhagic thrombocythemia

Chronic Myeloproliferative Disorders

Thrombocytosis

Neoplasm Metastasis

Thrombocythemia, Hemorrhagic

Acute myeloid leukemia, adult

Congenital Abnormalities

Acute myelocytic leukemia

Polycythemia Vera

Myelodysplastic syndromes

Essential thrombocytosis

Myelofibrosis

Hematologic Diseases

Myelodysplastic Syndromes

Myelodysplasia

Myeloproliferative Disorders

Acute myelogenous leukemia

Fludarabine monophosphate

Polycythemia vera

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Fludarabine

Bone Marrow Diseases

Additional relevant MeSH terms:

Antimetabolites

Disease

Neoplasms by Histologic Type

Antimetabolites, Antineoplastic

Immunologic Factors

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Physiological Effects of Drugs

Immunosuppressive Agents

Pharmacologic Actions

Neoplasms

Pathologic Processes

Therapeutic Uses

Syndrome

ClinicalTrials.gov processed this record on August 21, 2008

Sponsored by:	Baylor College of Medicine
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00069992