Bone Marrow Transplant Plus Cyclophosphamide and Total-Body Irradiation in Treating Patients With Hematologic Cancer - Full Text View

Sponsored by:	Fox Chase Cancer Center CCOP Research Base
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002809

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy and radiation therapy together with bone marrow transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bone marrow transplant from an unrelated donor together with cyclophosphamide and total-body irradiation works in treating patients with hematologic cancer.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: anti-thymocyte globulin Biological: filgrastim Biological: sargramostim Biological: therapeutic immune globulin Drug: cyclophosphamide Drug: methotrexate Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Unrelated Bone Marrow Transplantation With Cyclophosphamide and Total Body Irradiation For Hematologic Malignancies and Bone Marrow Failure States

Resource links provided by NLM:

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

Drug Information available for: Cyclophosphamide Methotrexate Tacrolimus anhydrous Tacrolimus Filgrastim Sargramostim Immunoglobulins Globulin, Immune

U.S. FDA Resources

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

Estimated Enrollment:	10
Study Start Date:	August 1996

Detailed Description:

OBJECTIVES:

Study the curative potential of high-dose cyclophosphamide and total-body irradiation followed by rescue with bone marrow from volunteer HLA-matched donors in patients with a variety of hematologic malignancies and bone marrow failure states.
Study the toxic effects associated with matched unrelated bone marrow transplantation in this patient population.
Participate in collaborative research studies with the National Marrow Donor Program.

OUTLINE: All patients receive myeloablative therapy with high-dose cyclophosphamide and total body irradiation over 4 days; patients with severe aplastic anemia also receive antithymocyte globulin. Patients then undergo allogeneic bone marrow transplantation. Filgrastim (G-CSF) is given after transplant to accelerate engraftment. Sargramostim (GM-CSF) may be given in case of graft failure.

All patients receive graft-versus-host-disease (GVHD) prophylaxis with tacrolimus, methotrexate, and gamma globulin. Established GVHD is treated with corticosteroids and, as necessary, antithymocyte globulin.

Patients are followed at 100 days, 6 months, and 1 year after transplant, then annually thereafter.

PROJECTED ACCRUAL: A total of 10 patients per year will be accrued for this study over 5 years.

Eligibility

Ages Eligible for Study:	17 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

One of the following hematologic malignancies/disorders:
- Acute lymphoblastic leukemia
  - In second or subsequent complete remission (CR)
  - In first CR with high-risk features (e.g., Philadelphia chromosome-positive)
  - In first relapse and failed conventional salvage therapy
- Acute myelogenous leukemia (AML)
  - In second or subsequent CR
  - In early first relapse
  - In full first relapse and failed conventional salvage therapy
  - In first CR with high-risk features, e.g., trisomy 8 or FAB 6/7
    - Standard-risk AML offered conventional-dose consolidation chemotherapy or autologous bone marrow transplantation
- Chronic myelogenous leukemia in chronic, accelerated, or second chronic phase
  - No blast crisis
- Severe aplastic anemia that has failed at least 1 course of immunosuppressive therapy
- Paroxysmal nocturnal hemoglobinuria with high-risk features (e.g., disseminated intravascular coagulation, thrombotic events)
- Myelodysplastic syndrome, i.e.:
  - Symptomatic, transfusion-dependent refractory anemia with excess blasts
  - (RAEB) or RAEB in transformation
- Secondary leukemia in CR following conventional-dose induction chemotherapy
Unrelated marrow donor available who is 8 out of 10-, 9 out of 10-, or 10 out of 10-antigen serologically HLA-matched at A, B, C, DRb, and DQB loci by molecular typing
No CNS malignancy

PATIENT CHARACTERISTICS:

Age:

17 to 60

Performance status:

Karnofsky 70-100%

Life expectancy:

No reduction due to other serious illness

Hematopoietic:

Not specified

Hepatic:

Bilirubin less than 3 mg/dL
AST/ALT no greater than twice normal

Renal:

Creatinine no greater than 2.0 mg/dL
Creatinine clearance greater than 60 mL/min

Cardiovascular:

Left ventricular ejection fraction at least 45%
No severe hypertension

Pulmonary:

DLCO, FEV_1, and FVC at least 50%

Other:

HIV negative
No active infection at time of transplant
No advanced diabetes
No significant neurologic deficit
No active drug or substance abuse
No emotional disorders
Able to participate in frequent medical care for at least 1-2 years
Willing to comply with National Marrow Donor Program policies

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

See Disease Characteristics

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002809

Locations

United States, Pennsylvania
Fox Chase-Temple Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2442

Sponsors and Collaborators

Fox Chase Cancer Center CCOP Research Base

Investigators

Study Chair:

Kenneth F. Mangan, MD, FACP

Fox Chase Cancer Center CCOP Research Base

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

Study ID Numbers:	CDR0000064937, TUHSC-2803, NCI-V96-0950
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00002809 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
refractory chronic lymphocytic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
refractory anemia
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation

secondary acute myeloid leukemia
previously treated myelodysplastic syndromes
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)

Study placed in the following topic categories:

Tacrolimus
Refractory Anemia
Preleukemia
Acute Myelocytic Leukemia
Anemia, Refractory
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasm Metastasis
Methotrexate
Rho(D) Immune Globulin
Myelodysplastic Myeloproliferative Disease
Immunoglobulins
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

Myeloproliferative Disorders
Pancytopenia
Leukemia, Myeloid
Folic Acid
Leukemia, Myeloid, Accelerated Phase
Immunoglobulins, Intravenous
Chronic Myelogenous Leukemia
Antimetabolites
Leukemia, Lymphoid
Precancerous Conditions
Hematologic Neoplasms
Immunologic Factors
Folate
Leukemia, Myeloid, Chronic-Phase
Cyclophosphamide

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Cyclophosphamide
Tacrolimus
Leukemia
Preleukemia
Pathologic Processes
Therapeutic Uses
Syndrome

Abortifacient Agents
Methotrexate
Rho(D) Immune Globulin
Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Immunoglobulins
Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal

ClinicalTrials.gov processed this record on July 02, 2009