Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Diseases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT00453206
First received: March 27, 2007
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and melphalan, before a donor peripheral stem cell transplant or bone marrow transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus, methotrexate, mycophenolate mofetil, and antithymocyte globulin before and after transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer or abnormal cells as not belonging in the patient's body and destroy them (graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with hematologic cancer or other diseases.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients With Hematological Diseases

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • Treatment-related Mortality Within the First 6 Months After Transplantation [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete Response [ Time Frame: monthly ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: monthly ] [ Designated as safety issue: No ]
  • Disease-free Survival [ Time Frame: monthly ] [ Designated as safety issue: No ]
  • Graft-versus-host Disease [ Time Frame: monthly ] [ Designated as safety issue: No ]
  • Iron Status at the Time of Transplantation [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Quality of Life at the Time of Transplantation [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Treatment-related Mortality at 100 Days After Transplantation [ Time Frame: 100 days ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: February 2007
Study Completion Date: August 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the feasibility (i.e., risk of treatment-related mortality during the first 6 months after transplantation) of administering reduced-intensity allogeneic hematopoietic stem cell transplantation to patients with hematologic cancer or other diseases.

Secondary

  • Determine the response rate (partial and complete response), 6- and 12-month probabilities of response, and time to progression in patients treated with this regimen.
  • Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
  • Determine other toxicities of this regimen in these patients.
  • Determine the overall survival and disease-free survival of patients treated with this regimen.
  • Determine the impact of iron status on overall and disease-free survival.
  • Determine the influence of quality of life (at time of transplantation) on overall survival.

OUTLINE:

  • Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3. Patients also receive busulfan IV over 2 hours every 6 hours on days -4 and -3 or melphalan IV over 2 hours on day -3.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients with matched related donors receive oral tacrolimus twice daily on days -1 to 90 followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6. Patients with matched unrelated and 9/10 matched related donors receive oral tacrolimus twice daily on days -1 to 180 followed by a taper; methotrexate IV on days 1, 3, 6, and 11; and oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper. All patients also receive antithymocyte globulin IV over 4 to 6 hours once a day on days -4 to -1.
  • Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) beginning on day 7 and continuing until blood counts recover.
  • Lymphocyte infusion: Patients with progressive or stable disease while off immunosuppression and no active GVHD may receive up to 3 donor lymphocyte infusions from the original donor at 8-week intervals beginning on day 180 or 210 .

Quality of life is assessed at baseline.

After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed hematological disease, including any of the following:

    • Chronic lymphocytic leukemia

      • Absolute lymphocytosis > 5,000/µL
      • Morphologically mature lymphocytes with < 55% prolymphocytes
      • Lymphocyte phenotype with expression of CD19 and CD5
      • Absence of CD23 expression allowed provided disease is morphologically distinguished from mantle cell lymphoma
    • Prolymphocytic leukemia

      • Absolute lymphocytosis > 5,000/µL
      • Morphologically mature lymphocytes with > 55% prolymphocytes
    • Non-Hodgkin's or Hodgkin's lymphoma

      • Any WHO classification histologic subtype
      • Diagnosis by core biopsy allowed provided there is adequate tissue for diagnosis and immunophenotyping
      • Diagnosis by bone marrow biopsy not acceptable for follicular lymphomas
    • Multiple myeloma

      • Has received ≥ 1 prior treatment regimen
      • Has a partial response or greater by the Blade Criteria
      • Patients who achieved complete remission are eligible
    • Acute myeloid leukemia

      • Documented control (i.e., < 10% bone marrow blasts and no circulating blasts)
    • Myelodysplastic syndromes

      • Documented disease as defined by WHO or French-American-British Cooperative group criteria
      • Chronic myelogenous leukemia
    • Patients with atypical chronic myelogenous leukemia (i.e., absent Philadelphia chromosome) are eligible
    • Polycythemia vera

      • Documented disease as defined by WHO criteria (i.e., A1 + A2, and any other category A, OR A1 + A2, and any 2 category B):

        • A1: Total red blood cell mass > 25% above mean normal predicted value OR hemoglobin > 18.5 g/dL in males, 16.5 g/dL in females (hematocrit ≥ 60% in males or ≥ 56% in females)
        • A2: No cause of secondary erythrocytosis (absence of familial erythrocytosis, no elevation of epoetin alfa [EPO] due to hypoxia, high oxygen affinity hemoglobin, truncated EPO receptor, or inappropriate ectopic EPO production)
        • A3: Splenomegaly
        • A4: Clonal genetic abnormality other than the Philadelphia chromosome
        • A5: Endogenous erythroid colony formation in vitro
        • B: Platelet count > 400,000/mm³, WBC > 12,000/mm³, bone marrow biopsy with prominent erythroid and megakaryocytic proliferation, and low serum EPO
    • Chronic idiopathic myelofibrosis

      • Documented disease as defined by WHO criteria
      • Must have a HLA-identical donor, a matched unrelated donor, or a HLA 9/10 related donor meeting the following criteria:
      • HLA-identical sibling (6/6)

        • Serologic typing for class I (A, B)
        • Molecular typing for class II (DRB1)
      • 9/10 matched related donor

        • High-resolution molecular typing at HLA-A, B, C, DRB1, and DQB1
        • Only a single mismatch at one class I or II allele allowed
      • 10/10 matched unrelated donor

        • Molecular identity at HLA-A, B, C, DRB1, and DQB1 by high-resolution typing
        • Syngeneic donors are not eligible
  • Creatinine clearance ≥ 40 mL/min
  • Bilirubin ≤ 3 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN
  • DLCO ≥ 40% with no symptomatic pulmonary disease
  • LVEF ≥ 30% by cardiac MRI or echocardiogram with no symptomatic cardiac disease
  • Fertile patients willing to use effective contraception

Exclusion Criteria:

  • Uncontrolled diabetes mellitus
  • Active serious infection
  • Known hypersensitivity to E. coli-derived products
  • Known HIV positivity
  • History of another malignancy*, meeting the following criteria:

    • Non-skin malignancy or melanoma within the past 5 years
    • Concomitant malignancy that has not been curatively treated
    • NOTE: *However, cancer survivors who have undergone potentially curative therapy for a prior malignancy at least 5 years before enrollment and are deemed at low risk of < 30% for recurrence by their treating physicians is considered
  • Pregnant or nursing
  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: NCT00453206

Locations
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Study Chair: David Hurd, MD Wake Forest Baptist Health
  More Information

Additional Information:
No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT00453206     History of Changes
Other Study ID Numbers: CDR0000538185, CCCWFU-29506, IRB00001366
Study First Received: March 27, 2007
Results First Received: May 28, 2014
Last Updated: September 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Comprehensive Cancer Center of Wake Forest University:
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)
accelerated phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
blastic phase chronic myelogenous leukemia
primary myelofibrosis
chronic phase chronic myelogenous leukemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
de novo myelodysplastic syndromes
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
previously treated myelodysplastic syndromes
prolymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Lymphoma
Leukemia
Syndrome
Myeloproliferative Disorders
Plasmacytoma
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

ClinicalTrials.gov processed this record on October 01, 2014