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

• ClinicalTrials.gov Identifier: NCT00068523
• Recruitment Status: Completed
• First Posted: September 11, 2003
• Last Update Posted: July 27, 2020
• Sponsor: Case Comprehensive Cancer Center
• Information provided by: Case Comprehensive Cancer Center

Tracking Information

• First Submitted Date: September 10, 2003
• First Posted Date: September 11, 2003
• Last Update Posted Date: July 27, 2020
• Study Start Date: June 2003
• Actual Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 19, 2010): Study the effectiveness of combining ultraviolet-B light therapy with allogeneic stem cell transplantation in treating patients who have hematologic malignancies. [ Time Frame: Patients are followed at least monthly for 3 months and then at 6, 12, 18, and 24 months. ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ultraviolet-B Light Therapy and Allogeneic Stem Cell Transplantation in Treating Patients With Hematologic Malignancies
• Official Title: Immunomodulation by Ultraviolet B-Irradiation (UVB) to Facilitate Allogeneic Stem Cell Transplantation for Treatment of Hematologic Malignancies

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.

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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

Intervention

• Biological: anti-thymocyte globulin
  anti-thymocyte globulin IV over 4 hours on days -2 to -1
• Drug: cyclophosphamide
  cyclophosphamide IV over 1 hour on days -3 to -2
• Drug: cyclosporine
  oral cyclosporine on days -1 to 100
• Drug: fludarabine phosphate
  fludarabine IV over 30 minutes on days -8 to -4
• Drug: methylprednisolone
  methylprednisolone (oral or IV) on days 5-15
• Procedure: UV light therapy
  Patients undergo ultraviolet-B (UVB) light therapy every other day between days -10 and -2 for a total of 3 days. 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.
• Procedure: allogeneic bone marrow transplantation
• Procedure: peripheral blood stem cell transplantation
  Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo PBSC transplantation on day 0.

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 19, 2010): 10
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00068523
• Other Study ID Numbers: ICC7Y02
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Omer N. Koc, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
• Study Sponsor: Case Comprehensive Cancer Center
• Collaborators: Not Provided

Investigators

• Principal Investigator: Omer N. Koc, MD; Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

• PRS Account: Case Comprehensive Cancer Center
• Verification Date: July 2020