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Phase I Study of T Cell Depleted (TCD) Partially Matched Related Donor (PMRD) Hematopoietic Stem Cell Transplantation for High Risk Hematologic Diseases Using Intense Pre and Post Transplant Immunosuppression and Megadose CD34 "Veto" Cells


Phase 1
N/A
45 Years
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Precancerous/Nonmalignant Condition, Small Intestine Cancer

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Trial Information

Phase I Study of T Cell Depleted (TCD) Partially Matched Related Donor (PMRD) Hematopoietic Stem Cell Transplantation for High Risk Hematologic Diseases Using Intense Pre and Post Transplant Immunosuppression and Megadose CD34 "Veto" Cells


OBJECTIVES: I. Determine if megadose CD34 cells and intense immunosuppression administered
before and after partially matched related donor (PMRD) hematopoietic stem cell (HSC)
transplantation results in engraftment in patients with high risk hematologic malignancies.
II. Determine the incidence and severity of acute grade (I-IV) and chronic (limited or
extensive) graft versus host disease in patients after rigorous T-cell depletion in PMRD HSC
transplantation.

OUTLINE: Harvest: Bone marrow and peripheral blood stem cells (PBSC) are harvested from a
related 1, 2, or 3 HLA antigen mismatched donor. PBSC are selected for CD34+ cells and
T-cells are depleted. Conditioning: Patients undergo total body irradiation twice daily on
days -10 to -7 and once on day -6. Patients receive cladribine IV continuously on days -10
to -6; etoposide IV over 2 hours on day -5; and cyclophosphamide IV over 2 hours,
antithymocyte globulin (ATG) IV over 10-12 hours, and methylprednisolone IV over 1 hour on
days -4 to -2. Transplantation: T-cell depleted PBSC and bone marrow are infused on day 0.
Patients receive G-CSF SQ daily beginning on day 0 and continuing until blood counts
recover. Graft versus host disease prophylaxis: Patients receive tacrolimus IV every 12
hours beginning on day -2 and continuing orally 4 times a day for 6-12 months at the
discretion of the protocol investigator. Patients receive ATG IV over 10-12 hours and
methylprednisolone IV over 1 hour on days 5-15 followed by a taper of methylprednisolone.
Patients are followed every week through day 100 and then at 6 and 12 months.

PROJECTED ACCRUAL: A total of 12-20 patients will be accrued for this study within 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically proven hematologic malignancy with relapse after
allogeneic bone marrow transplantation (BMT) or autologous BMT if no HLA matched sibling
donor is available OR Histologically proven acute myeloid leukemia (AML) without an
available HLA matched sibling donor and with one of the following: Failure of induction,
defined as inability to obtain remission with 2 courses of induction or failure during
treatment Second or greater remission OR Histologically proven acute lymphocytic leukemia
(ALL) in an adult over age 15 without an available HLA matched sibling donor and with one
of the following: Philadelphia chromosome positivity by cytogenetics or PCR Relapse or
second or greater remission Two or more prognostic features (over age 30, WBC on
presentation over 35,000/mm3, time to complete response over 4 weeks, t(4:11), or B-cell
ALL) OR Histologically proven chronic myelogenous leukemia In chronic phase without an A,
B, and DR unrelated matched donor OR In accelerated phase, defined as new cytogenetic
abnormalities or difficulty maintaining a normal WBC due to dose limiting cytopenias
(thrombocytopenias or anemia) from hydroxyurea or interferon OR In blast transformation OR
Histologically proven aplastic anemia without an available HLA matched sibling donor and
failure of an immunosuppressive therapy regimen using either cyclosporine, antithymocyte
globulin, or both OR Histologically proven lymphoma without an available HLA matched donor
and failure of at least 2 different chemotherapy regimens OR Histologically proven
cutaneous T-cell lymphoma without an available HLA matched donor and failure of interferon
and PUVA (psoralen and ultraviolet A radiation) OR Histologically proven myelodysplastic
syndrome without an available HLA matched sibling donor and with one of the following: 5%
or greater blasts in marrow Multiple cytogenetic abnormalities History of infections from
neutropenia 1, 2, or 3 antigen mismatched related donor available

PATIENT CHARACTERISTICS: Age: Physiologic age 45 and under Performance status: ECOG 0-2
Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic:
Bilirubin no greater than 2.0 mg/dL SGOT and SGPT no greater than 2 times upper limit of
normal Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No myocardial
infarction within the past 6 months No coronary artery disease requiring medical therapy
Resting LVEF at least 40% Pulmonary: FEV1/FVC at least 60% predicted DLCO at least 60%
predicted Other: HIV negative No prior malignancy except basal cell or squamous cell skin
cancer Other malignancies for which the patient is cured by local surgical therapy, such
as head and neck cancer or stage I breast cancer, are considered on an individual basis
Not pregnant Negative pregnancy test Fertile patients must use effective contraception No
psychiatric illness or mental deficiency that would preclude compliance or informed
consent

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See
Disease Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified
Surgery: Not specified

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Richard K. Burt, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Robert H. Lurie Cancer Center

Authority:

United States: Federal Government

Study ID:

NU FDA97H1

NCT ID:

NCT00004904

Start Date:

October 1999

Completion Date:

July 2000

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Precancerous/Nonmalignant Condition
  • Small Intestine Cancer
  • monoclonal gammopathy of undetermined significance
  • stage III cutaneous T-cell non-Hodgkin lymphoma
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • isolated plasmacytoma of bone
  • extramedullary plasmacytoma
  • refractory multiple myeloma
  • Waldenstrom macroglobulinemia
  • stage III multiple myeloma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood acute myeloid leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • small intestine lymphoma
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • adult acute myeloid leukemia in remission
  • adult acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • polycythemia vera
  • chronic idiopathic myelofibrosis
  • essential thrombocythemia
  • refractory hairy cell leukemia
  • T-cell large granular lymphocyte leukemia
  • acute undifferentiated leukemia
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III adult Burkitt lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV adult Burkitt lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult Burkitt lymphoma
  • stage III adult T-cell leukemia/lymphoma
  • stage IV adult T-cell leukemia/lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • secondary acute myeloid leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • graft versus host disease
  • primary systemic amyloidosis
  • intraocular lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent childhood large cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • recurrent mantle cell lymphoma
  • stage III mycosis fungoides/Sezary syndrome
  • stage IV mycosis fungoides/Sezary syndrome
  • recurrent mycosis fungoides/Sezary syndrome
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage III marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • stage IV marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • childhood myelodysplastic syndromes
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Precancerous Conditions
  • Lymphoma, Large-Cell, Immunoblastic
  • Duodenal Neoplasms
  • Ileal Neoplasms
  • Jejunal Neoplasms
  • Intestinal Neoplasms

Name

Location

Robert H. Lurie Comprehensive Cancer Center, Northwestern UniversityChicago, Illinois  60611