Umbilical Cord Blood (UCB) Transplant, Fludarabine, Melphalan, and Anti-thymocyte Globulin (ATG) in Treating Patients With Hematologic Cancer

This study has been terminated.
(Unacceptable morbidity & mortality)
Sponsor:
Information provided by (Responsible Party):
Northside Hospital, Inc.
ClinicalTrials.gov Identifier:
NCT00827099
First received: January 21, 2009
Last updated: March 19, 2012
Last verified: March 2012
  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
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: umbilical cord blood transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Northside Hospital, Inc.:

Primary Outcome Measures:
  • Number of Participants With 100 Day Transplant-related Mortality (TRM) [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    100 Day TRM is death within 100 days from transplant related complications


Secondary Outcome Measures:
  • Number of Patients That Engrafted Blood Counts by 30 Days After Transplant [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
    Number of patients whose Absolute Neutrophil Count (ANC) recovered to >500 x10^3/uL for at least 3 consecutive days after transplant

  • Percentage of Donor and Host Chimerism of Each Cord Blood Unit [ Time Frame: day 30, day 60, day 90 ] [ Designated as safety issue: Yes ]
    Evaluate the percentages of donor and host chimerism at multiple times post-transplant including Day 30, Day 60, Day 90 and monthly thereafter if the patient is not considered to have full chimerism.

  • Number of Patients Who Experience Acute and Chronic Graft-vs-host Disease After Transplant. [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
    Patients will be evaluated regularly for the development of graft versus host disease both acute & chronic.

  • Number of Patients Who Experience Disease Relapse Post-transplant [ Time Frame: Day 100, 6 months, 1 year, 18 months, 24 months ] [ Designated as safety issue: No ]
    Patients will have routine restaging to assess disease response at Day 100, 6 months, 1 year, 18 months and 24 months. If disease relapse is suspected, the patient will be evaluated at that time.

  • Number of Patients Who Survive Following Treatment on This Protocol [ Time Frame: Through Death ] [ Designated as safety issue: No ]
    Patients will be followed until death


Enrollment: 5
Study Start Date: June 2006
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: anti-thymocyte globulin
    anti-thymocyte globulin
    Drug: fludarabine phosphate
    fludarabine phosphate
    Drug: Melphalan
    melphalan
    Drug: mycophenolate mofetil
    mycophenolate mofetil
    Drug: tacrolimus
    tacrolimus
    Procedure: umbilical cord blood transplantation
    umbilical cord blood transplantation
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 cytometry, 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
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: NCT00827099

Locations
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
Sponsors and Collaborators
Northside Hospital, Inc.
Investigators
Principal Investigator: Scott R. Solomon, MD Blood and Marrow Transplant Group of Georgia
  More Information

No publications provided

Responsible Party: Northside Hospital, Inc.
ClinicalTrials.gov Identifier: NCT00827099     History of Changes
Other Study ID Numbers: CDR0000632453, BMTGG-NSH-801
Study First Received: January 21, 2009
Results First Received: July 28, 2011
Last Updated: March 19, 2012
Health Authority: United States: Federal Government

Keywords provided by Northside Hospital, Inc.:
accelerated phase cml
adult ALL in remission
adult AML in remission
adult AML with 11q23 (MLL) abnormalities
adult AML 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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Lymphoma
Leukemia
Syndrome
Neoplasms by Histologic Type
Neoplasms
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
Tacrolimus
Fludarabine phosphate
Mycophenolate mofetil
Melphalan

ClinicalTrials.gov processed this record on September 16, 2014