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T Cell-Reduced Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation With Pentostatin and Low-Dose Total Body Irradiation


Phase 1/Phase 2
19 Years
75 Years
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes, Nonmalignant Neoplasm

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Trial Information

T Cell-Reduced Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation With Pentostatin and Low-Dose Total Body Irradiation


OBJECTIVES:

Primary

- To determine the safety of pentostatin and low-dose total body irradiation followed by
T-cell-reduced unrelated donor peripheral blood stem cell transplantation, in terms of
regimen-related toxicity, in patients with hematological malignancies.

- To evaluate the efficacy of this regimen, measured as engraftment rate and
establishment of donor hematopoietic chimerism, in these patients.

Secondary

- To determine the incidence of acute and chronic graft-versus-host disease in patients
treated with this regimen.

OUTLINE:

- Reduced-intensity preparative regimen: Patients receive pentostatin IV over 30 minutes
once daily on days -10 to -8 and undergo low-dose total-body irradiation on day -1.

- Unrelated donor peripheral blood stem cell transplantation (PBSCT): Patients undergo
T-cell-reduced donor PBSCT on day 0.

- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2
hours twice daily on days -1, 0, and 1 and then orally twice daily on days 2-70
followed by a taper in the absence of GVHD. Patients also receive oral mycophenolate
mofetil twice daily on days 0-27 followed by a taper.

Patients undergo bone marrow aspirate and biopsies and blood sample collection periodically
for laboratory studies. Samples are analyzed for cytokines (i.e., IL-6, TNF-γ, IL-1β, and
IL-10) by ELISA; phenotypic, molecular, and functional analysis of immunologic
reconstitution markers (i.e., PHA, IL-2, IL-4, IL-10, IL-12, Fas, FasL, TNF, TGF-β, and
IFN-γ) by flow cytometry; and cytogenetics by FISH.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of a confirmed hematological malignancy that has relapsed or is at high
risk for relapsing, including any of the following:

- Acute myeloid leukemia (AML) meeting any of the following criteria:

- Antecedent hematologic disorder

- Therapy related

- Primary induction failure

- In first complete remission (CR1) with poor-risk cytogenetics, as defined
by the following:

- del(5q)/-5

- del(7q)/-7

- abn(3q)

- t(6;9)

- del(20q)

- del(17p)

- +13

- Complex karyotype

- t(9;22) = 11q23 rearrangement

- In second complete remission (CR2) or greater

- Acute lymphoblastic leukemia meeting any of the following criteria:

- In CR1 with WBC > 50,000/mm³ at diagnosis

- In CR1 with poor-risk cytogenetics (i.e., t[9;22], t[1;19], t[4;11]) AND
meets at least 1 of the following criteria:

= 19-75 years of age AND received prior high-dose chemotherapy, total-body irradiation
(TBI), or a radiation dose that precludes administration of 12 Gy of TBI = 50-75 years of
age = 19-75 years of age with hematopoietic stem cell transplantation (HSCT) comorbidity
index ≥ 3

- CNS or testicular involvement at diagnosis

- No CR within 4 weeks of initial treatment

- Primary induction failure

- In CR2 or greater

- Myelodysplastic syndromes meeting the following criteria:

- Intermediate-2 or high-risk category as determined by International Prognostic
Scoring System

- Not considered a candidate for intensive or standard chemotherapy or HSCT

- Chronic myelogenous leukemia meeting any of the following criteria:

- First chronic phase AND < 40 years of age

- First chronic phase AND no hematologic response after 3 months of imatinib mesylate
therapy

- First chronic phase AND never achieved a complete cytogenetic response during
imatinib mesylate therapy

- First chronic phase AND loss of previously documented response

- Accelerated phase

- Blast crisis phase

- Chronic myeloproliferative disorder (i.e., polycythemia vera, essential
thrombocythemia, myelofibrosis)

- Bone marrow blasts > 5% and/or other evidence of progression to acute leukemia

- Chronic myelomonocytic leukemia

- Severe aplastic anemia

- Failed prior antithymocyte globulin and cyclosporine immunosuppressive therapy

- Mantle cell lymphoma meeting any of the following criteria:

- In CR1

- In first partial remission (PR1)

- In CR 2 or greater

- In second PR (PR2) or greater

- Indolent non-Hodgkin lymphoma OR chronic lymphocytic leukemia meeting either of
the following criteria:

- In CR 2 or greater

- In PR 2 or greater

- Lymphoblastic lymphoma

- In CR1 or greater

- Must have minimal residual disease as defined by either of the following:

- No more than 5% blasts in blood and/or bone marrow (in patients with acute
leukemia/MDS)

- No bulky adenopathy (> 5 cm masses) and/or < 20% bone marrow involvement by
lymphoma (in patients with lymphoma)

- No progressive disease within 8 weeks of most recent prior therapy OR within 12
weeks of prior autologous HSCT

- No active CNS malignancy (i.e., known positive CSF cytology or parenchymal
lesions visible by CT scan or MRI)

- HLA-matched unrelated peripheral blood stem cell donor available

- Meets the University of Nebraska Medical Center's or the National Marrow
Donor Program's criteria for donors

- Matched at 7/8 or 8/8 HLA-A, B, C, or DRβ1 loci by molecular typing

- If match is not at allele level, suitability for donation requires discussion with
and approval by the principal investigator

- Not an identical twin

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Creatinine clearance ≥ 55 mL/min

- Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert's
disease or malignancy)

- ALT and AST ≤ 4 times ULN

- DLCO ≥ 40%

- FEV1/FVC ratio ≥ 50% of predicted

- Cardiac ejection fraction ≥ 40%

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Not receiving supplementary continuous oxygen

- No NYHA grade II-IV cardiac disease

- HIV negative

- No evidence of active hepatitis B (i.e., positive HBsAg and/or positive HBeAg or high
copy number on quantitative RNA testing) or hepatitis C

- No active uncontrolled infection or immediate life-threatening condition

- No uncontrolled medical illnesses (e.g., uncontrolled systemic hypertension or
diabetes)

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Prior cytoreductive chemotherapy or irradiation to areas of bulky disease allowed, as
determined by the primary physician in consultation with the study investigators

- No other concurrent anti-tumor therapy

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Severe transplant-related toxicity (grade III-IV adverse events) as assessed by NCI CTCAE v2.0

Outcome Time Frame:

before day 100

Safety Issue:

Yes

Principal Investigator

Robert Bociek, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Nebraska

Authority:

United States: Institutional Review Board

Study ID:

164-07

NCT ID:

NCT00816413

Start Date:

September 2008

Completion Date:

February 2010

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Nonmalignant Neoplasm
  • 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)
  • adult acute myeloid leukemia in remission
  • recurrent adult acute myeloid leukemia
  • secondary acute myeloid leukemia
  • adult acute lymphoblastic leukemia in remission
  • recurrent adult acute lymphoblastic leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • chronic myelomonocytic leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • essential thrombocythemia
  • polycythemia vera
  • primary myelofibrosis
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • aplastic anemia
  • chronic eosinophilic leukemia
  • chronic neutrophilic leukemia
  • contiguous stage II adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • stage I adult diffuse small cleaved cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • contiguous stage II grade 1 follicular lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • stage I grade 1 follicular lymphoma
  • stage I grade 2 follicular lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • contiguous stage II marginal zone lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • stage I marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • contiguous stage II small lymphocytic lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • stage I small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • contiguous stage II mantle cell lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • stage I mantle cell lymphoma
  • contiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • stage I adult lymphoblastic lymphoma
  • stage I chronic lymphocytic leukemia
  • stage II chronic lymphocytic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders

Name

Location

UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680