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Peripheral Blood Stem Cell Allotransplantation for Hematological Malignancies Using a Positive Stem Cell Selection Technique for T-Cell Depletion, Followed by Delayed T-Cell Add-Back


Phase 2
10 Years
75 Years
Open (Enrolling)
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Secondary Myelofibrosis, Small Intestine Cancer

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Trial Information

Peripheral Blood Stem Cell Allotransplantation for Hematological Malignancies Using a Positive Stem Cell Selection Technique for T-Cell Depletion, Followed by Delayed T-Cell Add-Back


OBJECTIVES:

- Determine the overall survival rate at day 200 in patients with hematologic cancers or
other diseases who undergo allogeneic peripheral blood stem cell transplantation using
the CliniMACS® CD34 Reagent System for T-cell depletion followed by delayed T-cell
add-back.

- Determine the safety of this regimen, in terms of the nonrelapse mortality rate at day
200, in these patients.

OUTLINE:

- Myeloablative preparative regimen: Patients receive fludarabine phosphate IV over 30
minutes on days -8 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2.
Patients also undergo high-dose* total body irradiation (TBI) twice daily on days -7 to
-4.

NOTE: *Patients over 55 years of age receive reduced-dose TBI.

- Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients receive
T-cell-depleted (via the CliniMACS® CD34 Reagent System), filgrastim (G-CSF)-mobilized,
donor PBSC IV over 4 hours on day 0.

- Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine (or
tacrolimus) IV or orally twice daily on days -6 to 21, and then again beginning on day
89 and continuing up to day 150, followed by a slow taper to day 180, in the absence of
GVHD.

- Donor lymphocyte infusion (DLI): Patients receive delayed T-cell add-backs of donor
lymphocytes IV over 1 hour on day 90. If relapse occurs, patients may receive DLI
before day 90 or as a repeat infusion.

After completion of study therapy, patients are followed periodically for 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of 1 of the following:

- Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

- Under 21 years of age and in chronic phase

- Ten to 75 years of age with CML in chronic phase, meeting 1 of the
following criteria:

- Failed or intolerant to prior treatment with imatinib mesylate

- No prior therapeutic doses of imatinib mesylate within 12 months after
disease diagnosis

- Ten to 75 years of age with CML in accelerated phase or blast
transformation

- Acute lymphoblastic leukemia, meeting 1 of the following criteria:

- In first remission with any of the following high-risk features:

- WBC > 100,000/mm³ at diagnosis

- Karyotypes t9; 22, t4, t19, t11, or biphenotypic leukemia

- In second or subsequent remission

- Primary induction failure

- Partially responding or untreated relapsed disease

- Acute myeloid leukemia (AML), meeting 1 of the following criteria:

- In first remission

- No AML with good-risk karyotypes (e.g., M3 [t15; 17], M4Eo [inv 16], t
[8; 21])

- In second or subsequent remission

- Primary induction failure

- Resistant relapsed disease

- Myelodysplastic syndromes (MDS), including any of the following subtypes:

- Refractory anemia with transfusion dependence

- Refractory anemia with excess blasts

- MDS in transformation to acute leukemia

- Chronic myelomonocytic leukemia

- Atypical MDS/myeloproliferative disorders

- Myeloproliferative disorders, including any of the following subtypes:

- Atypical (Philadelphia chromosome negative) chronic myelogenous or
neutrophilic leukemias

- Progressing myelofibrosis

- Polycythemia vera

- Essential thrombocythemia in transformation to acute leukemia

- Essential thrombocythemia with progressive transfusion requirements or
pancytopenia

- Chronic lymphocytic leukemia

- Refractory to fludarabine phosphate treatment AND meets 1 of the following
criteria:

- Bulky progressive disease

- Thrombocytopenia (i.e., platelet count ≤ 100,000/mm^3) not due to
recent chemotherapy

- Anemia (i.e., hemoglobin ≤ 10 g/dL) not due to recent chemotherapy

- Non-Hodgkin's lymphoma, including mantle cell lymphoma, that has relapsed or is
refractory to standard-of-care treatments

- Multiple myeloma or Waldenstrom's macroglobulinemia that is unresponsive to or
relapsed after standard-of-care treatments

- HLA-identical (6/6) related donor available

PATIENT CHARACTERISTICS:

- Life expectancy ≥ 3 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No major anticipated illness or organ failure incompatible with survival from
transplantation

- No severe psychiatric illness or mental deficiency that would preclude study
compliance

- HIV negative

- DLCO ≥ 65% of predicted

- LVEF ≥ 40%

- AST ≤ 20 times upper limit of normal (ULN)

- Bilirubin ≤ 10 times ULN

- Creatinine ≤ 6 times ULN

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior allogeneic stem cell transplantation

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival at day 200

Safety Issue:

No

Principal Investigator

Aarthi Shenoy, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Heart, Lung, and Blood Institute (NHLBI)

Authority:

Unspecified

Study ID:

CDR0000512813

NCT ID:

NCT00398346

Start Date:

September 2006

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • Secondary Myelofibrosis
  • Small Intestine Cancer
  • graft versus host disease
  • secondary myelofibrosis
  • de novo myelodysplastic syndromes
  • Philadelphia chromosome negative chronic myelogenous leukemia
  • refractory anemia with excess blasts
  • refractory anemia
  • refractory anemia with excess blasts in transformation
  • previously treated myelodysplastic syndromes
  • atypical chronic myeloid leukemia, BCR-ABL negative
  • chronic neutrophilic leukemia
  • primary myelofibrosis
  • polycythemia vera
  • essential thrombocythemia
  • stage III multiple myeloma
  • refractory multiple myeloma
  • Waldenstrom macroglobulinemia
  • refractory chronic lymphocytic leukemia
  • childhood chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • blastic 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)
  • adult acute myeloid leukemia in remission
  • recurrent adult acute myeloid leukemia
  • childhood acute myeloid leukemia in remission
  • recurrent childhood acute myeloid leukemia
  • secondary acute myeloid leukemia
  • secondary myelodysplastic syndromes
  • adult acute lymphoblastic leukemia in remission
  • recurrent adult acute lymphoblastic leukemia
  • childhood acute lymphoblastic leukemia in remission
  • recurrent childhood acute lymphoblastic leukemia
  • adult grade III lymphomatoid granulomatosis
  • adult nasal type extranodal NK/T-cell lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • intraocular lymphoma
  • nodal marginal zone B-cell lymphoma
  • primary central nervous system non-Hodgkin lymphoma
  • 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 immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic 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
  • small intestine lymphoma
  • splenic marginal zone lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • childhood grade III lymphomatoid granulomatosis
  • childhood nasal type extranodal NK/T-cell lymphoma
  • recurrent childhood grade III lymphomatoid granulomatosis
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • chronic myelomonocytic leukemia
  • accelerated phase chronic myelogenous leukemia
  • Burkitt lymphoma
  • childhood diffuse large cell lymphoma
  • childhood immunoblastic large cell lymphoma
  • chronic phase chronic myelogenous leukemia
  • myelodysplastic/myeloproliferative neoplasm, unclassifiable
  • stage I multiple myeloma
  • stage II multiple myeloma
  • childhood myelodysplastic syndromes
  • Primary Myelofibrosis
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Duodenal Neoplasms
  • Ileal Neoplasms
  • Jejunal Neoplasms
  • Intestinal Neoplasms
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location
NIH - Warren Grant Magnuson Clinical Center Bethesda, Maryland  20892-1182