Clinical trial NCT00062140: Total-Body Irradiation, Cyclophosphamide, and Stem Cell Transplantation in Treating Patients With Hematologic Cancer
Official title: A Phase I Trial Of Total Body Irradiation, Cyclophosphamide Dose-Adjustment Based On Its Metabolism, And Hematopoietic Stem Cell Transplantation For Patients With Hematological Malignancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Keywords: recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
recurrent mycosis fungoides/Sezary syndrome
secondary acute myeloid leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III mantle cell lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV mantle cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
recurrent adult acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
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)
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-06-06
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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 effect on the body of dose-adjusted cyclophosphamide combined with total-body irradiation and donor stem cell transplantation in treating patients who have hematologic cancer.

Detailed description: 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 daily until day 80 after transplantation and then regularly thereafter for survival.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* 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 irraditation 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:

Age

* 18 to 65

Performance status

* Not specified

Life expectancy

* Not severely limited by diseases other than malignancy
* Not moribund

Hematopoietic

* Not specified

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

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics
* No prior radiotherapy to the liver or adjacent organs

Surgery

* Not specified

Other

* No concurrent aspirin or nonsteroidal anti-inflammatory medications such as ibuprofen (e.g., Motrin® or Advil®)
* No other concurrent phase I study enrollment

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: George B. McDonald, MD
role: STUDY_CHAIR
References: