Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 17 to 60 Other TUHSC-2803 NCI-V96-0950, NCT00002809

Objectives

1. 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.
2. Study the toxic effects associated with matched unrelated bone marrow transplantation in this patient population.
3. Participate in collaborative research studies with the National Marrow Donor Program.

Entry 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

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

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, FEV₁, 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Fox Chase Cancer Center CCOP Research Base

Kenneth Mangan, MD, FACP, Protocol chair		Ph: 215-214-3129 Email: mangank@tuhs.temple.edu

Registry Information
Official Title		Unrelated Bone Marrow Transplantation With Cyclophosphamide and Total Body Irradiation For Hematologic Malignancies and Bone Marrow Failure States
Trial Start Date		1996-08-02
Registered in ClinicalTrials.gov		NCT00002809
Date Submitted to PDQ		1996-08-02
Information Last Verified		2005-08-20