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Phase II Feasibility Study of T-Cell Depletion in Allogeneic Unrelated Bone Marrow Transplantation (MUD ALLO BMT) Followed by Delayed T-Cell Infusions


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Malignant Plasma Cell Neoplasms, Myelodysplastic Syndromes, Precancerous Condition, Secondary Myelofibrosis

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Trial Information

Phase II Feasibility Study of T-Cell Depletion in Allogeneic Unrelated Bone Marrow Transplantation (MUD ALLO BMT) Followed by Delayed T-Cell Infusions


OBJECTIVES:

Primary

- Determine if T-cell depletion of a peripheral blood progenitor cell (PBPC) graft
followed by delayed add-backs of defined doses of donor lymphocytes decreases the rate
of graft-versus-host disease and its complications in matched unrelated donor (MUD)
allogeneic PBPC transplantation in patients with hematologic cancers or other diseases.

- Determine whether targeted T-cell dosages in the PBPC graft can be achieved in these
patients by positive CD34+ selection using the Baxter Inc. Isolex 300i v. 2.5.

- Determine the effects of T-cell depletion on the rate of engraftment in these patients.

- Develop a MUD allogeneic transplantation regimen that will decrease overall
treatment-related mortality in these patients.

OUTLINE: This is a non-randomized study.

- Myeloablative preparative regimen: Patients receive cyclophosphamide IV once daily on
days -5 and -4 followed by total body irradiation twice daily on days -3, -2, and -1.
Patients also receive tacrolimus on day -1 administered by continuous IV infusion over
24 hours.

- Peripheral blood progenitor cell graft transplantation: Patients receive T-cell
depleted, peripheral blood progenitor cells (PBPC) by IV infusion on day 0. Beginning 1
day after completion of the PBPC infusion, patients receive filgrastim (G-CSF)
subcutaneously once daily until blood counts recover.

- Post transplantation T cell add-backs: Patients receive defined doses of donor T cells
by IV infusion on days 45 and 100, in the absence of active graft-versus-host disease
(GVHD) requiring steroids*.

NOTE: *A T cell add-back may be given in the presence of GVHD, if the investigator considers
the risk from relapse or overwhelming viral infection to outweigh the risk of exacerbating
GVHD.

Patients will be followed periodically for relapse and survival.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of any of the following hematologic cancers or other diseases:

- Acute myelogenous leukemia

- Relapsed or refractory disease with poor-risk cytogenetics

- Acute lymphoblastic leukemia

- Relapsed or refractory disease with poor-risk cytogenetics

- Chronic myelogenous leukemia

- Persistent disease after at least 6 months of treatment with imatinib
mesylate (Gleevec)

- Myelodysplasia, meeting 1 of the following criteria:

- French-American-British Classification of refractory anemia with excess
blasts (RAEB) or RAEB with transformation

- International Prognostic Scoring System score > 2

- Lymphoid malignancies, including non-Hodgkin lymphoma, Hodgkin disease, chronic
lymphocytic leukemia, and prolymphocytic leukemia

- Relapsed or refractory disease after at least 1 prior therapy

- Myelofibrosis

- Transfusion dependent (RBC's, platelets, or both)

- Paroxysmal nocturnal hemoglobinuria (transfusion dependent)

- Myeloproliferative disorder

- Eosinophilic leukemia

- Severe aplastic anemia

- Corrected reticulocyte count < 1%

- Platelet count < 30,000/mm³ (untransfused)

- Bone marrow biopsy with < 15% cellularity

- Plasma cell leukemia

- No essential thrombocytopenia or polycythemia vera

- No matched related donor available

- Must have an 8/8 or 7/8 serologic HLA matched unrelated donor available

PATIENT CHARACTERISTICS:

- Cardiac ejection fraction ≥ 45% (if < 45%, then cardiac consult required)

- Not pregnant or nursing

- Negative pregnancy test

- FEV_1 and DLCO ≥ 45% predicted

- Creatinine < 2.0 mg/dL

- Bilirubin < 2.0 mg/dL

- HIV negative

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior allogeneic bone marrow transplantation

- No concurrent administration of steroids with T-cell add-backs

INCLUSION CRITERIA:

- Patient actual weight must not be greater than 1.5x their ideal body weight

- Cardiac ejection fraction >45%. If less than 45%, a Cardiac consult will be
obtained.

- A suitably matched unrelated donor that is at least a 7 out of 8 HLA serologic match.

- Patient is not pregnant.

- FEV 1 and DLCO > 45% predicted on pulmonary function testing.

- Serum creatinine <2.0 mg/dl, serum bilirubin <2.0 mg/dl.

- Patient and donor are HIV negative.

- Diagnosis of one of the following diseases

- Acute myelogenous leukemia

- Relapsed disease,

- Refractory disease, or

- With poor-risk cytogenetics

- Acute lymphoblastic leukemia

- Relapsed disease,

- Refractory disease, or

- With poor-risk cytogenetics

- Chronic myelogenous leukemia

- Persistent disease after at least 6 months of treatment with Imatinib Mesylate
(Gleevec)

- Myelodysplasia

- FAB Classification of RAEB or RAEB-T -Or-

- IPSS score >2

- Lymphoid malignancies, including non-Hodgkin's lymphoma, Hodgkin's disease, chronic
lymphocytic leukemia and prolymphocytic leukemia

- Relapsed or refractory disease after at least 1 prior therapy

- Myelofibrosis

- Transfusion dependence (RBC's, platelets, or both)

- Paroxysmal Nocturnal Hemoglobinuria (PNH)

- Transfusion dependent

- Myeloproliferative Disorder

- Eosinophilic Leukemia

- Severe aplastic anemia (<1% corrected reticulocyte count, <30,000 untransfused
platelet count, bone marrow biopsy with <15% cellularity)

- Plasma cell leukemia

- Patients with ET or PV will not be candidates unless their disease has transformed to
end stage myelofibrosis or acute leukemia, for which eligibility criteria for
myelofibrosis or acute leukemia would apply.

- Patient must signed written informed consent.

EXCLUSION CRITERIA:

- Inability to give informed consent

- Absence of any of the above mentioned medical conditions

- Availability of matched-related donor

- History of prior allogeneic BMT

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment-related mortality (TRM)

Outcome Time Frame:

TRM

Safety Issue:

Yes

Principal Investigator

Brian J. Bolwell, MD

Investigator Role:

Study Chair

Investigator Affiliation:

The Cleveland Clinic

Authority:

United States: Federal Government

Study ID:

CASE-CCF-6501

NCT ID:

NCT00589602

Start Date:

January 2004

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Malignant Plasma Cell Neoplasms
  • Myelodysplastic Syndromes
  • Precancerous Condition
  • Secondary Myelofibrosis
  • Adult luekemias
  • lymphoma
  • myelodysplastic syndromes
  • plasma cell disorders
  • Primary Myelofibrosis
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Precancerous Conditions

Name

Location

Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195