Fludarabine, Melphalan, Total-Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

Fludarabine, Melphalan, Total-Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders
This study is ongoing, but not recruiting participants.

First Received on March 4, 2009.  
Last Updated on May 30, 2012  
History of Changes
Sponsor: Roswell Park Cancer Institute
Information provided by (Responsible Party): Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00856388
  Purpose

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It may also stop the patient’s immune system from rejecting the donor’s stem cells. The donated stem cells may replace the patient’s immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well giving fludarabine and melphalan together with total-body irradiation followed by donor stem cell transplant works in treating patients with hematologic cancer or bone marrow failure disorders.

Condition Intervention Phase
Chronic Myeloproliferative Disorders
Fanconi Anemia
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Nonmalignant Neoplasm
Paroxysmal Nocturnal Hemoglobinuria
Biological: anti-thymocyte globulin
Biological: graft-versus-tumor induction therapy
Drug: fludarabine phosphate
Drug: melphalan
Procedure: allogeneic hematopoietic stem cell transplantation
Radiation: total-body irradiation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial of Reduced Intensity Allogeneic Stem Cell Transplantation With Fludarabine, Melphalan, and Low Dose Total Body Irradiation

Resource links provided by NLM:

Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:

  • Transplant-related mortality rate by day 100 [ Time Frame: DAY 100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

  • Time to engraftment [ Time Frame: day 30, day 60 and day 100 ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: weekly until day 100 ] [ Designated as safety issue: Yes ]
  • Clinical response [ Time Frame: day 100 ] [ Designated as safety issue: No ]
  • Rate of complete donor chimerism [ Time Frame: day 30,day 100 ] [ Designated as safety issue: No ]
  • Acute and chronic graft-vs-host disease [ Time Frame: day 30, day 60, day 100 and yearly ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Yearly ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: January 2009
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Intervention Details:

    Biological: anti-thymocyte globulin

    IV over 3 days

    Biological: graft-versus-tumor induction therapy

    PO every 12 hours or iv equivalent, from day -1.

    Drug: fludarabine phosphate

    IV over 30 minutes

    Drug: melphalan

    IV over 30 minutes

    Procedure: allogeneic hematopoietic stem cell transplantation

    IV day 0

    Radiation: total-body irradiation

    day -1

Detailed Description:

OBJECTIVES:

Primary

  • To determine the transplant-related mortality in patients with hematologic malignancies or bone marrow failure disorders treated with reduced-intensity conditioning regimen comprising fludarabine phosphate, melphalan, and low-dose total-body irradiation followed by allogeneic stem cell transplantation.

Secondary

  • To evaluate the time to engraftment in patients treated with this regimen.
  • To evaluate the safety of this regimen in these patients.
  • To evaluate the clinical response in patients treated with this regimen.
  • To evaluate the graft-vs-malignancy effect of this regimen in these patients.
  • To evaluate the evidence of graft-vs-host disease in patients treated with this regimen.
  • To evaluate the overall outcomes of patients treated with this regimen.

OUTLINE: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo low-dose total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

NOTE: *Patients with chromosomal breakage syndromes or debilitated patients do not receive melphalan; instead, they receive anti-thymocyte globulin IV over 4 hours on day -4 to -2.

After completion of study therapy, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   3 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed hematologic malignancy or marrow disorder.

    • Bone marrow failure disorders and other non-malignant Hematologic or immunologic disorders:

      • Severe aplastic anemia that has failed at least 1 course of standard immunosuppressive therapy with calcineurin inhibitor and anti-thymocyte globulin OR has a fully-matched donor available
      • Paroxysmal nocturnal hemoglobinuria (PNH) with a history of thrombosis related to PNH
      • Fanconi anemia or related chromosomal breakage syndrome as confirmed by diepoxybutane or mitomycin C testing
    • Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), meeting the following criteria:

      • Ineligible for conventional myeloablative stem cell transplantation
      • Resistant or recurrent disease after at least 1 standard combination chemotherapy regimen OR in first remission and is at high risk of relapse as defined by 1 of the following:

        • AML with antecedent myelodysplastic syndromes (MDS)
        • Secondary AML
        • AML with high-risk cytogenetic abnormalities
        • AML with normal cytogenetics AND high-risk molecular mutations (NPM1, Flt3-ITD mutation, CEBPA)
        • High- or standard-risk ALL
    • Chronic myeloid leukemia, meeting 1 of the following criteria:

      • In chronic phase AND is intolerant or unresponsive to imatinib mesylate and/or other tyrosine kinase inhibitors
      • In second chronic phase or accelerated phase AND is not eligible for conventional myeloablative stem cell transplantation
    • Myeloproliferative disorders or MDS, including any of the following:

      • Myelofibrosis (with or without splenectomy) with intermediate- to high-risk features
      • MDS with an IPSS score of intermediate-2 or higher
      • Chronic myelomonocytic leukemia
    • Lymphoproliferative disease, including any of the following:

      • Recurrent or persistent chronic lymphocytic leukemia or low-grade non-Hodgkin lymphoma (NHL) that is refractory to fludarabine OR had a complete remission that lasted < 6 months between courses of conventional therapy
      • Multiple myeloma

        • Progressive disease after autologous stem cell transplantation
        • Tandem allogeneic transplant after prior autologous stem cell transplant
      • Waldenstrom macroglobulinemia that failed one standard regimen
      • High-grade NHL or diffuse large B-cell lymphoma
      • Lymphoproliferative disease that is not eligible for conventional myeloablative stem cell transplantation OR failed autologous stem cell transplantation
      • Lymphoblastic lymphoma, small non-cleaved cell lymphoma, or mantle cell lymphoma in first remission
    • Hodgkin lymphoma, meeting the following criteria:

      • Failed front-line therapy
      • Failed or was not eligible for autologous stem cell transplantation
  • No uncontrolled CNS disease (for hematologic malignancies)
  • Has an HLA-matched donor available, meeting the following criteria:

    • Related donor matched at 5 of 6 HLA antigens
    • Unrelated donor with a single antigen mismatch at HLA-A, -B, or -C (with or without additional single allele level mismatch)

      • Must have at least an antigen-level match at DRB1
    • Cord blood donor with ≥ 4 out of 6 antigen match at HLA-A, -B, and -DRB1 antigens
    • No syngeneic donors

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 50-100% (for patients > 16 years of age)
  • Lansky performance status 50-100% (for patients ≤ 16 years of age)
  • Bilirubin < 3 times upper limit of normal (ULN)
  • Alkaline phosphatase < 3 times ULN
  • SGOT/SGPT < 3 times ULN
  • Creatinine clearance ≥ 30 mL/min
  • LVEF ≥ 35%
  • DLCO ≥ 40% predicted (corrected for hemoglobin and/or alveolar ventilation)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening
  • No serious uncontrolled psychiatric illness
  • No HIV positivity
  • No Child’s Pugh class B and C liver failure
  • No concurrent active malignancy other than nonmelanoma skin cancer
  • No uncontrolled diabetes mellitus or cardiovascular disease
  • No active serious infection or other condition that, in the opinion of treating physician, would make this study unreasonably hazardous for the patient

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 90 days since prior autologous or myeloablative allogeneic bone marrow transplantation
  • At least 2 weeks since prior chemotherapy, radiotherapy, and/or surgery
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00856388

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00856388    
History of Changes
Other Study ID Numbers: I 118807
Study First Received: March 4, 2009
Last Updated: May 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:

recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell 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
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
accelerated phase chronic myelogenous leukemia
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)
atypical chronic myeloid leukemia
childhood chronic myelogenous leukemia

Additional relevant MeSH terms:

Anemia
Neoplasms
Fanconi Anemia
Fanconi Syndrome
Hemoglobinuria
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Hemoglobinuria, Paroxysmal
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Lymphoma, Large-Cell, Immunoblastic
Myelodysplastic-Myeloproliferative Diseases
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Kidney Diseases
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Metabolism, Inborn Errors
Proteinuria
Urination Disorders

ClinicalTrials.gov processed this record on August 21, 2012

Leave a Reply

You can use these HTML tags

<a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>

  

  

  

13 − thirteen =