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Chemotherapy and Total-Body Irradiation Followed by Donor Umbilical Cord Blood Transplant, Cyclosporine, and Mycophenolate Mofetil in Treating Patients With Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00290641
First received: February 9, 2006
Last updated: October 9, 2012
Last verified: October 2012
  Purpose

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, 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 the transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving chemotherapy together with total-body irradiation followed by donor umbilical cord blood transplant, cyclosporine, and mycophenolate mofetil works in treating patients with hematologic cancer.


Condition Intervention
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Myelodysplastic Syndromes
Biological: filgrastim
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: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Cyclophosphamide/Fludarabine/Total Body Irradiation Preparative Regimen for Patients With Hematological Malignancy Receiving Unrelated Donor Umbilical Cord Blood Transplantation

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Engraftment as measured by an absolute neutrophil count of donor origin > 0.5 x 109 /L for 3 days by day 42 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and severity of acute or chronic graft-versus-host-disease, relapse, or mortality at day 100 [ Designated as safety issue: No ]
  • Survival and event-free survival by Kaplan-Meier estimation at 1 and 2 years after umbilical cord blood (UCB) transplant [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: April 2001
Study Completion Date: January 2006
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the engraftment potential of unrelated allogeneic umbilical cord blood (UCB) using nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil in patients with hematologic malignancies.

Secondary

  • Determine the rate of neutrophil and platelet recovery and the completeness of donor cell engraftment in patients treated with this regimen.
  • Determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients treated with this regimen.
  • Determine the incidence of malignant relapse in patients treated with this regimen.
  • Determine the 1- and 2-year survival and event-free survival of patients treated with this regimen.
  • Determine the phenotype and function of immune cells recovering after UCB transplantation in patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: Patients are stratified according to HLA disparity (0-1 vs 2) and number of graft units (1 vs 2).

  • Nonmyeloablative conditioning: Patients receive nonmyeloablative conditioning comprising fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total-body irradiation twice daily on days -4 to -1.
  • Unrelated allogeneic umbilical cord blood transplantation (UCBT): Patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
  • Immunosuppression: Patients receive cyclosporine orally or IV over 2 hours 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper in the absence of graft-vs-host disease (GVHD). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 30, continuing beyond day 30 if no donor engraftment. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of a hematologic malignancy of 1 of the following types:

    • Acute myeloid leukemia (AML), meeting the following criteria:

      • In complete remission (CR) by morphology (< 5% blasts in the bone marrow), as defined by 1 of the following:

        • In first CR (CR1) and meets ≥ 1 of the following high-risk criteria:

          • High-risk cytogenetics (e.g., those associated with myelodysplastic syndromes [MDS] or complex karotype)
          • Preceding MDS
          • More than 2 courses of therapy was required to obtain CR
        • In second or greater CR
      • No morphologic relapse

        • Cytogenetic relapse or persistent disease allowed
    • Acute lymphocytic leukemia (ALL), meeting the following criteria:

      • In CR, as defined by 1 of the following:

        • In CR1 and meets ≥ 1 of the following high-risk criteria:

          • Unfavorable high-risk cytogenetics [t(9;22), t(1;19), t(4;11) or other MLL rearrangements]
          • More than 1 course of therapy was required to obtain CR
        • In second or greater CR
      • No morphologic relapse or persistent disease
    • Chronic myelogenous leukemia (CML), excluding refractory blast crisis
    • Advanced myelofibrosis
    • Advanced myelodysplasia (blasts < 10% [otherwise need AML induction pre-transplant]), meeting ≥ 1 of the following criteria:

      • Refractory anemia with excess blasts (RAEB)
      • RAEB in transformation
      • Refractory anemia with severe pancytopenia
      • High-risk cytogenetics
    • Non-Hodgkin's lymphoma (NHL), meeting the following criteria:

      • One of the following histologic subtypes:

        • Mantle cell NHL

          • Disease progression after initial therapy (e.g., CHOP)
          • Beyond CR1 or beyond first partial remission (PR)
        • Intermediate-grade NHL in second or greater CR or PR
        • High-grade NHL

          • Stage III or IV disease AND received initial therapy
          • Stage I or II disease at diagnosis that subsequently progressed after a prior response duration of < 1 year
      • No chemotherapy-refractory NHL (i.e., < progressive disease after > 2 salvage regimens)
  • Donor available, meeting the following criteria:

    • No other existing HLA-identical related donor available
    • 4-6/6 HLA-A, -B, and -DRB1, matched unrelated donor by molecular techniques

      • A and B to antigen level resolution
      • DR to allele resolution
    • Umbilical cord blood (UCB) graft may consist of one or two UCB units NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

  • Karnofsky score 80-100% (for adults) OR
  • Lansky score 50-100% (for children)
  • Creatinine ≤ 2.0 mg/dL (for adults) OR creatinine clearance > 40 mL/min (for children)

    • Adults with a creatinine > 1.2 mg/dL or a history of renal dysfunction must have a creatinine clearance > 40 mL/min
  • Bilirubin ≤ 2 times normal
  • AST and ALT ≤ 2 times normal
  • Alkaline phosphatase ≤ 2 times normal
  • Pulmonary function > 50 % of normal
  • LVEF ≥ 45%
  • No active infection, including Aspergillus or other mold, within the past 30 days
  • No history of HIV infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior myeloablative transplant within the past 6 months if ≤ 18 years old
  • No prior myeloablative allotransplant or autologous transplant if > 18 years old
  • No prior extensive therapy (e.g., > 12 months of alkylating therapy or > 6 months of alkylating therapy with extensive radiation)
  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: NCT00290641

Locations
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Claudio G. Brunstein, MD, PhD Masonic Cancer Center, University of Minnesota
  More Information

Publications:
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00290641     History of Changes
Other Study ID Numbers: 2000LS068, MT2000-25
Study First Received: February 9, 2006
Last Updated: October 9, 2012
Health Authority: United States: Federal Government

Keywords provided by Masonic Cancer Center, University of Minnesota:
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
childhood acute myeloid leukemia in remission
secondary acute myeloid leukemia
accelerated phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
refractory anemia with excess blasts
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
noncontiguous stage II adult Burkitt lymphoma
recurrent adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
recurrent adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma

Additional relevant MeSH terms:
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myeloproliferative Disorders
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Cyclophosphamide
Cyclosporine
Cyclosporins
Fludarabine
Fludarabine phosphate
Mycophenolate mofetil
Mycophenolic Acid
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on November 20, 2014