Total-body irradiation, cyclophosphamide, and stem cell transplantation in treating patients with hematologic cancer

Journal of Drugs in Dermatology, August, 2003

Sponsored by: Fred Hutchinson Cancer Research Center and National Cancer Institute (NCI)

RATIONALE: Adjusting the dose of drugs used in chemotherapy such as cyclophosphamide may decrease side effects while stopping cancer cells from dividing so they stop growing or die Radiation therapy uses high-energy x-rays to damage cancer cells Stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells

PURPOSE: Phase I trial to study the effectiveness of dose-adjusted cyclophosphamide combined with total-body irradiation and donor stem cell transplantation in treating patients who have hematologic cancer

Condition                   Treatment or Intervention    Phase

adult Hodgkin's lymphoma    Drug: cyclophosphamide       Phase I
adult acute lymphoblastic   Procedure: allogeneic bone
  leukemia                    marrow transplantation
adult acute myeloid         Procedure: biological
  leukemia                    response modifier
                              therapy
adult non-Hodgkin's         Procedure: bone marrow
  lymphoma                    ablation with stem
                              cell support
childhood acute myeloid     Procedure: bone marrow
  leukemia and other          transplantation
  myeloid malignancies
Chronic Myelogenous         Procedure: chemotherapy
  Leukemia
mycosis fungoides and       Procedure: peripheral
  Sezary syndrome             blood stem cell
                              transplantation
recurrent cutaneous         Procedure: radiation therapy
  T-cell lymphoma
secondary acute myeloid
  leukemia

Study Type: Interventional

Study Design: Treatment

OBJECTIVES:

* Determine a safe and reproducible method of adjusting the dose of cyclophosphamide based on its metabolism when given in combination with total body irradiation and hematopoietic stem cell transplantation in patients with hematologic malignancy.

OUTLINE:

* Preparative regimen: Patients undergo total body irradiation twice daily on days -6 to -4. Patients then receive dose-adjusted (based on metabolism) cyclophosphamide IV over 1 hour on days -3 and -2.

* Hematopoietic stem cell (HSC) infusion: Patients undergo allogeneic HSC transplantation on day 0. Patients receive graft-versus-host disease prophylaxis, CNS prophylaxis, and testicular irradiation as per institutional standard practices.

Patients are followed at days 28 and 75 and then regularly thereafter for survival.

Ages eligible for study: 18 years - 65 years, both genders

Inclusion Criteria:

DIAGNOSIS OF HEMATOLOGICAL MALIGNANCY, INCLUDING ANY OF THE FOLLOWING:

* Chronic myeloid leukemia

* Acute myeloid leukemia

* Acute lymphocytic leukemia

* Myelodysplastic syndromes

* Lymphoma

* Unlikely to respond to conventional treatment and would benefit from hematopoietic stem cell transplantation

* No bulky tumor mass requiring additional involved field radiotherapy

* No large body burden of tumor cells requiring cytoreductive chemotherapy before total body irradiation and cyclophosphamide

* Undergoing conditioning for transplantation at the University of Washington Medical Center

* Availability of 1 of the following types of allogeneic donors:

* HLA-identical family members

* Unrelated donors

* Allele match (match grade 1)

* One allele mismatch for A, B, C, DRB1 or DQB1 (match grades 2.1 or 2.2)

* Patient Characteristics:

* Life expectancy

* Not severely limited by diseases other than malignancy

* Not moribund

Hepatic

* Bilirubin no greater than 1.2 mg/dL

* No cirrhosis

* No hepatic fibrosis with bridging

Renal

* Creatinine no greater than 1.2 mg/dL

Cardiovascular

* No coronary artery disease

* No congestive heart failure requiring therapy

Pulmonary

* Oxygen saturation at least 93% (on room air)

Other

* Not pregnant or nursing

* Fertile patients must use effective contraception

* HIV negative

* No concurrent infection requiring systemic antibiotic or antifungal therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior hematopoietic stem cell transplantation

Radiotherapy

* No prior radiotherapy to the liver or adjacent organs

Other

* No concurrent aspirin or nonsteroidal anti-inflammatory medications such as ibuprofen (e.g., Motrinr or Advilr)

* No other concurrent phase I study enrollment

Location and Contact Information

Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109-1024, United States; George B. McDonald, MD, Study Chair, Fred Hutchinson Cancer Research Center Tel: 206-667-6932

Washington

A total of 20 patients will be accrued for this study.

Study ID Numbers CDR0000304522; FHCRC-1797.00

NLM Identifier NCT00062140