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

Sponsor:	Temple University
Information provided by:	Temple University
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:	Masking: Open Label Primary Purpose: Treatment
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: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Anemia Bone Marrow Transplantation Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Cyclophosphamide Methotrexate Granulocyte-macrophage colony-stimulating factor Tacrolimus anhydrous Tacrolimus Filgrastim Sargramostim Lenograstim Granulocyte colony-stimulating factor Immunoglobulins Globulin, Immune

U.S. FDA Resources

Further study details as provided by Temple University:

Estimated Enrollment:	10
Study Start Date:	August 1996
Study Completion Date:	December 2003
Primary Completion Date:	December 2003 (Final data collection date for primary outcome measure)

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

Temple University

Investigators

Study Chair:

Kenneth F. Mangan, MD, FACP

Fox Chase Cancer Center

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:	Temple University Bone Marrow Transplant Program, Temple University Health Systems
ClinicalTrials.gov Identifier:	NCT00002809 History of Changes
Other Study ID Numbers:	CDR0000064937, TUHSC-2803, NCI-V96-0950
Study First Received:	November 1, 1999
Last Updated:	September 30, 2010
Health Authority:	United States: Federal Government

Keywords provided by Temple University:

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)

Additional relevant MeSH terms:

Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antilymphocyte Serum
Cyclophosphamide
Methotrexate
Tacrolimus
Antibodies

Immunoglobulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on February 12, 2012