Full Text View
Tabular View
No Study Results Posted
Related Studies
Umbilical Cord Blood Transplant, Fludarabine, Melphalan, and Antithymocyte Globulin in Treating Patients With Hematologic Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: January 21, 2009   Last Updated: July 10, 2009   History of Changes
Sponsored by: Blood and Marrow Transplant Group of Georgia
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00827099
  Purpose

RATIONALE: Giving low doses of chemotherapy before a donor umbilical cord blood transplant helps stop the growth of cancer 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 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 tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving umbilical cord blood transplant together with fludarabine, melphalan, and antithymocyte globulin works in treating patients with hematologic cancer.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Drug: melphalan
Drug: mycophenolate mofetil
Drug: tacrolimus
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: umbilical cord blood transplantation
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Transplantation of Two Partially Matched Umbilical Cord Blood Units Following Reduced Intensity Conditioning to Enhance Engraftment and Limit Transplant-Related Mortality in Adults With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of transplant-related mortality [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of engraftment [ Designated as safety issue: No ]
  • Degree of donor-host chimerism [ Designated as safety issue: No ]
  • Incidence of acute and chronic graft-vs-host disease [ Designated as safety issue: No ]
  • Incidence of relapse [ Designated as safety issue: No ]
  • Survival [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: June 2006
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the 100-day transplant-related (non-relapse) mortality in patients with hematologic malignancies undergoing reduced-intensity conditioning comprising fludarabine phosphate, melphalan, and anti-thymocyte globulin followed by sequential umbilical cord blood transplantation (UCBT) from 2 partially-matched unrelated donors.

Secondary

  • To evaluate the 12-month transplant-related (non-relapse) mortality.
  • To evaluate the days to neutrophil engraftment (ANC > 500/mm³).
  • To evaluate the days to platelet engraftment (platelet count > 20,000/mm³ [unsupported]).
  • To evaluate the risk of acute and chronic graft-vs-host disease.
  • To evaluate percent donor chimerism contribution of each cord unit.
  • To evaluate relapse rate.
  • To evaluate disease-free and overall survival.
  • To evaluate transfusion support needed for UCBT recipients.

OUTLINE:

  • Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3, melphalan IV over 30-60 minutes on day -2, and anti-thymocyte globulin IV over 4-6 hours on days -4 to -2.
  • Transplantation: Patients undergo two sequential umbilical cord blood transplantations on day 0.
  • Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously and then orally twice daily beginning on day -1 and continuing until day 60, followed by a taper until day 180 in the absence of GVHD.

Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day 0 and continuing until day 30, followed by a taper until day 60 in the absence of GVHD. After completion of study treatment, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of hematologic malignancy for which a reduced-intensity allogeneic stem cell transplantation is deemed clinically appropriate, including any of the following:

    • Chronic myelogenous leukemia, meeting one of the following criteria:

      • In first chronic phase AND failed imatinib mesylate therapy, defined as failure to obtain a hematologic remission by 3 months or major cytogenetic response (Ph+ cells < 35%) by 12 months, or demonstrated clonal evolution or disease progression while on therapy
      • In accelerated phase with < 15% blasts
      • In blast crisis that has entered into a second chronic phase following induction chemotherapy
    • Acute myelogenous leukemia, meeting one of the following criteria:

      • In second or subsequent completion remission*
      • Failed primary induction chemotherapy, but subsequently entered into a complete remission* with ≤ 2 subsequent re-induction chemotherapy treatment(s)
      • In first complete remission* with poor-risk cytogenetics NOTE: *Complete remission is defined as < 5% blasts in bone marrow, no definitive evidence of disease by morphology, flow cytometery, or genetic studies, and no circulating blasts. Neutrophil and platelet count recovery will not be required.
    • Acute lymphoblastic leukemia, meeting one of the following criteria:

      • In second or subsequent complete remission
      • In first complete remission AND t(9;22)
    • Myelodysplastic syndromes, meeting the following criteria:

      • High-risk disease, defined as International Prognostic Scoring System score of ≥ 1.5
      • Less than 10% blasts at the time of study enrollment
    • Chronic myelomonocytic leukemia

      • Less than 10% blasts at the time of study enrollment
    • Myeloid metaplasia with myelofibrosis with poor-risk features, meeting one of the following criteria:

      • Age < 55 years AND a Lille score of 1
      • Lille score of 2
      • Hemoglobin < 10 g/dL AND abnormal karyotype
    • Chronic lymphocytic leukemia/prolymphocytic leukemia, meeting all of the following criteria:

      • Rai stage I-IV disease
      • Failed ≥ 1 prior chemotherapy regimen, including fludarabine, or autologous stem cell transplantation
      • Chemosensitive or stable, non-bulky disease prior to transplant
      • Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens)
    • Low-grade B-cell non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma, follicular center [grade 1 or 2] lymphoma, or marginal zone lymphoma), meeting all of the following criteria:

      • Failed ≥ 1 prior chemotherapy regimen or autologous stem cell transplantation
      • Chemosensitive or stable, non-bulky disease prior to transplant
      • Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens)
    • Intermediate-grade B-cell or T-cell NHL or mantle cell NHL, meeting all of the following criteria:

      • Failed to achieve remission or recurred after either conventional chemotherapy or autologous stem cell transplantation
      • Chemosensitive, non-bulky disease prior to transplant
    • Hodgkin lymphoma, meeting all of the following criteria:

      • Relapsed after prior autologous stem cell transplantation or after ≥ 2 combination chemotherapy regimens AND ineligible for autologous peripheral blood stem cell transplantation
      • Chemosensitive, non-bulky disease prior to transplant
    • Multiple myeloma, meeting one of the following criteria:

      • Relapsed after autologous stem cell transplantation
      • Relapsed after conventional therapies AND not a candidate for autologous stem cell transplantation
  • No HLA-matched related or unrelated donor available
  • Has two umbilical cord blood units available that are matched at ≥ 4/6 HLA A, B, and DRB1 with the patient and with each other (HLA C and DQ will not be used in the match strategy)

    • Total combined nucleated cell dose from the 2 umbilical cord blood units must be > 3.7 x 10^7 nucleated cells/kg (pre-freeze dose) 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 performance status 80-100%
  • Adapted, weighted Charlson Comorbidity Index < 3
  • Serum creatinine ≤ 2.0 mg/dL
  • AST or ALT < 3 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN
  • Not pregnant or nursing
  • LVEF ≥ 40%
  • DLCO > 50%
  • No hypoxia at rest with oxygen saturation < 92% on room air (corrected with bronchodilator therapy)
  • No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral infection)
  • No active hepatitis B or C infection that, in the opinion of a gastroenterologist or the transplant committee, places the patient at moderate- to high-risk for developing severe hepatic disease
  • No HIV infection

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00827099

Locations
United States, Georgia
Blood and Marrow Transplant Group of Georgia Recruiting
Atlanta, Georgia, United States, 30342
Contact: Scott R. Solomon, MD     404-255-1930        
Sponsors and Collaborators
Blood and Marrow Transplant Group of Georgia
Investigators
Principal Investigator: Scott R. Solomon, MD Blood and Marrow Transplant Group of Georgia
  More Information

Additional Information:
No publications provided

Responsible Party: Blood and Marrow Transplant Group of Georgia ( Scott R. Solomon )
Study ID Numbers: CDR0000632453, BMTGG-NSH-801
Study First Received: January 21, 2009
Last Updated: July 10, 2009
ClinicalTrials.gov Identifier: NCT00827099     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
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)
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
prolymphocytic leukemia
recurrent adult T-cell leukemia/lymphoma
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult Hodgkin lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
cutaneous B-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
Waldenstrom macroglobulinemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

Study placed in the following topic categories:
Chronic Myelomonocytic Leukemia
Blast Crisis
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Tacrolimus
Follicular Lymphoma
Mycoses
Acute Myelocytic Leukemia
Preleukemia
Hemorrhagic Disorders
Leukemia, Prolymphocytic
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Mycophenolate mofetil
Neoplasm Metastasis
Lymphoma, Large-Cell, Anaplastic
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Myeloproliferative Disorders
Leukemia, Myeloid
Multiple Myeloma
Waldenstrom Macroglobulinemia
B-cell Lymphomas
Leukemia, Myeloid, Accelerated Phase
Leukemia, T-Cell

Additional relevant MeSH terms:
Antimetabolites
Melphalan
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Precancerous Conditions
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Tacrolimus
Hemostatic Disorders
Leukemia
Preleukemia
Hemorrhagic Disorders
Pathologic Processes
Therapeutic Uses
Syndrome
Mycophenolate mofetil
Cardiovascular Diseases
Alkylating Agents
Lymphoma
Immunoproliferative Disorders
Neoplasms by Histologic Type
Disease
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Vascular Diseases

ClinicalTrials.gov processed this record on September 11, 2009