Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing a Donor Umbilical Cord Blood Transplant for Hematologic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Rochester
Sponsor:
Information provided by (Responsible Party):
University of Rochester
ClinicalTrials.gov Identifier:
NCT00255684
First received: November 18, 2005
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and radiation therapy before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor umbilical cord blood transplant for hematologic cancer.


Condition Intervention
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Biological: graft-versus-tumor induction therapy
Drug: cyclophosphamide
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: umbilical cord blood transplantation
Radiation: radiation therapy

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Non-Myeloablative Conditioning and Unrelated Umbilical Cord Blood Transplantation for Children and Adults With Serious Oncohematologic Diseases

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Lymphoma, Small Cleaved-cell, Diffuse Lymphosarcoma B-cell Lymphomas Follicular Lymphoma Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Chronic Myelomonocytic Leukemia Acute Myeloid Leukemia, Adult Multiple Myeloma Acute Lymphoblastic Leukemia Cutaneous T-cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Hodgkin Lymphoma Mantle Cell Lymphoma Burkitt Lymphoma Children's Interstitial Lung Disease Lymphoma, Large-cell Lymphoblastic Lymphoma Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Hairy Cell Leukemia Homologous Wasting Disease Chronic Myeloproliferative Disorders Myelodysplastic/myeloproliferative Disease Mycosis Fungoides Acute Lymphoblastic Leukemia, Childhood Sezary Syndrome Acute Myeloid Leukemia, Childhood Small Non-cleaved Cell Lymphoma Hodgkin Lymphoma, Childhood Juvenile Myelomonocytic Leukemia Myelofibrosis Anaplastic Plasmacytoma
U.S. FDA Resources

Further study details as provided by University of Rochester:

Estimated Enrollment: 20
Study Start Date: December 2003
Detailed Description:

OBJECTIVES:

  • Determine the frequency, extent, and rate of donor (myeloid and lymphoid) engraftment in patients with serious hematologic malignancies treated with nonmyeloablative conditioning regimen comprising fludarabine, cyclophosphamide, and low-dose total-body irradiation followed by unrelated allogeneic umbilical cord blood transplantation and post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil.
  • Correlate clinical and umbilical cord blood-related factors with engraftment in patients treated with this regimen.
  • Determine transplant-related complications, in terms of toxicity, myelosuppression, infections, and acute and chronic graft-versus-host disease, in patients treated with this regimen.
  • Determine disease-free and overall survival of patients treated with this regimen.
  • Determine treatment-related mortality of patients treated with this regimen.

OUTLINE: This is a uncontrolled, pilot study.

  • Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes daily on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6 and undergo low-dose total-body irradiation (TBI) on day 0.
  • Unrelated allogeneic umbilical cord blood transplantation (UCBT): After completion of TBI, patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
  • Post-transplant immunosuppression: Patients receive oral or IV cyclosporine daily beginning on day -3 and continuing until day 180 and oral or IV mycophenolate mofetil twice daily on days 0-30.

Patients are followed periodically for 1 year after transplantation.

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

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic malignancies:

    • Acute myeloid leukemia (AML) with or without history of myelodysplastic syndromes, meeting 1 of the following criteria:

      • In first complete remission (CR-1) with unfavorable cytogenetics and/or achieved CR-1 after ≥ 1 course of induction therapy
      • Secondary or treatment-related AML
      • In second or further complete remission
      • Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts
    • Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

      • In CR-1 with unfavorable cytogenetics or elevated WBC at presentation OR failed to achieve CR-1 after ≥ 4 weeks of induction therapy
      • In second or further complete remission
      • Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts
    • Other acute leukemic variants allowed at the discretion of the principal investigator
    • Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

      • In first chronic phase AND refractory to or unable to tolerate imatinib mesylate
      • In second or further chronic phase
      • In first or second accelerated phase
    • Myelodysplastic syndromes with intermediate 2- or high-risk International Prognosis Scoring System (IPSS) score, including any of the following:

      • Refractory anemia
      • Refractory anemia with excess blasts
      • Chronic myelomonocytic leukemia
    • Myeloproliferative disorders with poor prognosis, including any of the following:

      • Myelofibrosis with myeloid metaplasia

        • No ≥ grade 3 myelofibrosis
      • Atypical CML
      • Juvenile myelomonocytic leukemia
    • Other clonal hemopathies with an accepted poor prognosis
    • Multiple myeloma with chromosome 13 abnormalities and/or progression after prior autologous bone marrow transplantation (BMT)
    • Chronic lymphocytic leukemia, meeting 1 of the following criteria:

      • Primary refractory OR relapsed and refractory disease (less than partial remission)
      • Relapsed twice on or after prior chemotherapy
    • Lymphoma, meeting both of the following criteria:

      • Hodgkin's or non-Hodgkin's lymphoma in > CR-1 OR failed primary induction
      • Chemosensitive disease, defined as > 50% reduction in mass size after the most recent chemotherapy
  • Must meet ≥ 1 of the following criteria:

    • Over 45 years of age
    • Has undergone prior autologous or allogeneic BMT
    • Charlson^ comorbidity score ≥ 2
  • Must have a high degree of tumor control (salvage therapy allowed)
  • At high risk for treatment-related mortality with a myeloablative conditioning regimen
  • No massive splenomegaly

    • Patients may become eligible after splenectomy or radiotherapy to the spleen
  • No 5/6 or 6/6 HLA-matched related donor available
  • No well-matched (i.e., ≥ 9/10 HLA match by high-resolution typing) unrelated donor available

PATIENT CHARACTERISTICS:

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • Transaminases ≤ 4 times ULN (unless due to underlying disease)

Renal

  • Creatinine clearance ≥ 50 mL/min

Cardiovascular

  • Ejection fraction ≥ 30%

Pulmonary

  • DCLO ≥ 35%

Other

  • Negative pregnancy test
  • No uncontrolled viral, bacterial, or fungal infection
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics

Chemotherapy

  • See Disease Characteristics

Radiotherapy

  • See Disease Characteristics

Other

  • At least 3 months since prior immunosuppressive therapy
  • At least 10 days since prior salvage therapy for patients not in at least morphologic or radiologic complete remission
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00255684

Locations
United States, New York
James P. Wilmot Cancer Center at University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Gordon L. Phillips, MD    585-275-4918      
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Gordon L. Phillips, MD James P. Wilmot Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: University of Rochester
ClinicalTrials.gov Identifier: NCT00255684     History of Changes
Other Study ID Numbers: CDR0000448637, URCC-U19403, URCC-RSRB-10063
Study First Received: November 18, 2005
Last Updated: October 14, 2013
Health Authority: United States: Wilmot Cancer Center Data Safety and Monitoring Committee

Keywords provided by University of Rochester:
myelodysplastic/myeloproliferative neoplasm, unclassifiable
graft versus host disease
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
childhood acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
childhood acute lymphoblastic leukemia in remission
recurrent childhood acute lymphoblastic leukemia
acute undifferentiated leukemia
accelerated phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
refractory anemia with excess blasts
refractory anemia
chronic myelomonocytic leukemia
atypical chronic myeloid leukemia, BCR-ABL1 negative
juvenile myelomonocytic leukemia
primary myelofibrosis
refractory hairy cell leukemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
refractory chronic lymphocytic leukemia
stage III adult Hodgkin lymphoma

Additional relevant MeSH terms:
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Graft vs Host Disease
Lymphoma
Leukemia
Syndrome
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphatic Diseases
Disease
Pathologic Processes
Cyclophosphamide
Fludarabine phosphate

ClinicalTrials.gov processed this record on October 01, 2014