Ultraviolet-B Light Therapy and Allogeneic Stem Cell Transplantation in Treating Patients With Hematologic Malignancies

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00068523

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor are rejected by the body's normal cells. Ultraviolet-B light therapy given before and after allogeneic stem cell transplantation may help prevent this from happening.

PURPOSE: Clinical trial to study the effectiveness of combining ultraviolet-B light therapy with allogeneic stem cell transplantation in treating patients who have hematologic malignancies.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: anti-thymocyte globulin Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: methylprednisolone Procedure: UV light therapy Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation	N/A

Detailed Description

OBJECTIVES:

Primary

Determine the safety of ultraviolet-B light therapy and allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies by demonstrating 100-day mortality no greater than 15% and 1-year mortality no greater than 40%.
Determine the frequency of treatment-related toxicity leading to death and frequency of disease relapse resulting in death in patients treated with this regimen.
Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen.

Secondary

Determine the rates of donor allogeneic hematologic engraftment in patients treated with this regimen.
Determine the rate and quality of immune reconstitution in the peripheral blood and the composition of immune cells in the skin before and after transplantation in these patients.
Determine the event-free and overall survival of patients treated with this regimen.

OUTLINE:

Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4 and cyclophosphamide IV over 1 hour on days -3 to -2. Patients also receive anti-thymocyte globulin IV over 4 hours on days -2 to -1. Patients undergo ultraviolet-B (UVB) light therapy every other day between days -10 and -2 for a total of 3 days.
Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo PBSC transplantation on day 0.
Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine on days -1 to 100 and methylprednisolone (oral or IV) on days 5-15.
Posttransplantation UVB light therapy: Following PBSC transplantation, patients undergo UVB light therapy twice weekly on week 1 (at least 1 day apart) and three times weekly on weeks 2-4.

Donor lymphocyte infusion is performed per institutional guidelines for patients in whom emerging donor chimerism post allogeneic PBSC transplantation is not progressing (consistently below 50% during first 3 months), for whom donor chimerism is receding (to below 25%) despite cessation of cyclosporine, or who relapse within 24 months after allografting.

Patients are followed at least monthly for 3 months and then at 6, 12, 18, and 24 months.

PROJECTED ACCRUAL: A total of 23-36 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Immunomodulation by Ultraviolet B-Irradiation (UVB) to Facilitate Allogeneic Stem Cell Transplantation for Treatment of Hematologic Malignancies

Study Start Date :

Jun 1, 2003

Actual Primary Completion Date :

Mar 1, 2004

Outcome Measures

Primary Outcome Measures

Study the effectiveness of combining ultraviolet-B light therapy with allogeneic stem cell transplantation in treating patients who have hematologic malignancies. [Patients are followed at least monthly for 3 months and then at 6, 12, 18, and 24 months.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of any of the following hematologic malignancies:
Acute myeloid leukemia (AML) meeting any of the following criteria:
First complete remission with high-risk karyotype
Translocations t(15;17) allowed only if failed first-line induction therapy OR molecular evidence of persistent disease exists
Translocations t(8;21) and inv(16) allowed only if failed first-line induction therapy
Second or subsequent complete remission
Minimal residual disease*
Acute lymphoblastic leukemia meeting any of the following criteria:
Failed induction therapy and has minimal residual disease* by salvage therapy
First complete remission with high-risk karyotype (e.g., t[4;11] or t[9;22])
Relapsed disease allowed provided a second or subsequent complete remission or minimal residual disease* is achieved
Chronic myelogenous leukemia meeting any of the following criteria:
Persistent or relapsed disease after 1 year of imatinib mesylate therapy
Accelerated phase or blast crisis
Blast crisis allowed after reinduction chemotherapy places disease in chronic phase
Myelodysplastic syndromes meeting any of the following criteria:
Refractory to medical management
Cytogenetic abnormalities predictive of transformation into acute leukemia, including 5q-, 7q-, monosomy 7 and trisomy 8, or evidence of evolution to AML (e.g., refractory anemia with excess blasts (RAEB) or RAEB in transformation)
Non-Hodgkin's lymphoma or Hodgkin's lymphoma meeting any of the following criteria:
Beyond first complete remission or failed primary induction therapy and demonstrated sensitivity to therapy during the 6 months before transplantation
Recurrent disease after autologous stem cell transplantation
Must be at least 3 months posttransplantation
Cyclin D1+ mantle cell lymphoma allowed after induction therapy and in first remission
Multiple myeloma meeting either of the following criteria:
Refractory or relapsed disease
Residual disease after autologous transplantation
Chronic lymphocytic leukemia (CLL) meeting all of the following criteria:
Peripheral blood absolute lymphocyte count greater than 5,000/mm^3
Small to moderate size lymphocytes and less than 55% pro-lymphocytes, atypical lymphocytes, or lymphoblasts morphologically
B-cell or T-cell
Myeloproliferative disorders, including myelofibrosis
Philadelphia negative
Availability of a HLA-A, B, and DR identical family donor OR HLA-A, B, and DR genetically matched unrelated donor
Must meet 1 of the following criteria:
At least 55 years of age at time of transplantation
Received extensive prior therapy (i.e., more than 1 year of alkylator therapy or more than 2 different prior salvage regimens) or stem cell transplantation with myeloablative conditioning (either autologous or allogeneic)
Presenting with comorbid condition (e.g., abnormal cardiac, pulmonary, or renal function and/or prior life-threatening infection) that precludes eligibility for enrollment in allogeneic transplantation protocols with full ablation conditioning
No active CNS disease NOTE: *Defined as having no circulating blasts, absolute neutrophil count greater than 1,000/mm3 and less than 10% blasts in bone marrow at least 3 weeks after last systemic chemotherapy

PATIENT CHARACTERISTICS:

Age

See Disease Characteristics
Over 18

Performance status

ECOG 0-2

Life expectancy

At least 3 months

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin no greater than 2.0 mg/dL
ALT/AST no greater than 4 times normal

Renal

See Disease Characteristics
Creatinine less than 2.0 mg/dL OR
Creatinine clearance at least 50 mL/min

Cardiovascular

See Disease Characteristics
Normal cardiac function by echocardiogram or radionuclide scan
Shortening fraction or ejection fraction at least 40% of normal

Pulmonary

See Disease Characteristics
DLCO at least 60%
FEV_1 greater than 50% of predicted
Pulse oximetry greater than 85%

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No uncontrolled active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
At least 2 weeks since prior biologic response modifiers, signal transduction inhibitors, or monoclonal antibodies

Chemotherapy

See Disease Characteristics
At least 4 weeks since prior systemic conventional chemotherapy

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

Recovered from prior therapy
No concurrent sun block/sunscreen or any cosmetic that may act as a sunscreen (e.g., lotion with SPF) on the days of scheduled ultraviolet-B light therapy