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Transplantation of HLA Haploidentical Marrow Cells After Ex Vivo Exposure to Recipient Alloantigen in Presence of CTLA4-Ig - A Phase II Study of Tolerance Induction in Donor T Cells by Blockade of the CD80/CD86:CD28 Costimulatory Signal


Phase 2
N/A
50 Years
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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Trial Information

Transplantation of HLA Haploidentical Marrow Cells After Ex Vivo Exposure to Recipient Alloantigen in Presence of CTLA4-Ig - A Phase II Study of Tolerance Induction in Donor T Cells by Blockade of the CD80/CD86:CD28 Costimulatory Signal


OBJECTIVES: I. Determine the incidence and severity of acute graft versus host disease after
transplantation of HLA haploidentical bone marrow preincubated with alloantigen and CTLA4-Ig
ex vivo in patients with hematologic malignancies. II. Determine the engraftment rate with
this treatment regimen in these patients. III. Determine the safety of this treatment
regimen in these patients. IV. Determine the incidence of infection and relapse after this
treatment regimen in these patients. V. Determine whether host specific tolerance develops
in these patients after receiving this treatment regimen.

OUTLINE: This is a multicenter study. Patients undergo leukapheresis to collect white blood
cells which are incubated with donor bone marrow cells in the presence of CTLA4-Ig for 36
hours. Patients undergo total body irradiation on days -7, -6, -5, and -4 and receive
cyclophosphamide IV on days -3 and -2. Patients with acute lymphocytic leukemia, prior
lymphoid blast crisis chronic myelogenous leukemia, high grade non-Hodgkin's leukemia (NHL),
intermediate grade NHL with prior marrow or extramedullary disease, or prior CNS leukemia
receive 2 doses of methotrexate intrathecally prior to bone marrow transplantation, and 4-6
doses following. Patients receive bone marrow transplantation on day 0; methotrexate IV on
days 1, 3, 6, and 11; and cyclosporine IV on days -1 to 50. Patients are followed weekly for
1 month, monthly for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 1-2 years.

Inclusion Criteria


DISEASE CHARACTERISTICS: Any of the following hematologic malignancies: Acute myelogenous
leukemia in second or greater remission or relapse High risk acute lymphoblastic leukemia
First complete remission with high risk cytogenetics [e.g., t(9;22), t(8;14), or t(4;11)]
or slow early response OR Any second or greater remission OR Relapse or induction failure
Relapsed non-Hodgkin's lymphoma (NHL) with chemotherapy sensitive disease Multiple myeloma
with chemotherapy sensitive disease Chronic lymphocytic leukemia with chemotherapy
sensitive disease Myelodysplastic syndrome Chronic myelogenous leukemia (CML) in
accelerated phase, blast phase, or remission after blast phase Juvenile CML Patients must
have haploidentical donors and meet the following criteria: Lack an HLA A, B, and DR
matched related donor Lack an HLA A, B, DRB1 matched or single allele mismatched unrelated
donor or for whom the following apply: High likelihood of rapid disease progression while
an unrelated donor search is in progress AND Review of the patient HLA typing, gene
frequency, results of the preliminary search and the donor pool suggest that a donor will
not be found within a suitable time frame Lack an HLA A, B, DRB1 matched cord blood unit
or lack a cord blood unit that has an adequate cell dose and is mismatched for 1-2 HLA A,
B, DRB1 Do not have an indication for autologous transplant, including patients with NHL
or multiple myeloma who are not eligible for autologous transplant Negative antidonor
antibody crossmatch

PATIENT CHARACTERISTICS: Age: Under 51 Performance status: Not specified Life expectancy:
No patients with life expectancy severely limited by diseases other than malignancy
Hematopoietic: See Disease Characteristics Hepatic: AST no greater than 2 times normal
Renal: Creatinine no greater than 2 times normal OR Creatinine clearance at least 50% for
age, weight, and height Cardiovascular: No cardiac insufficiency requiring treatment No
symptomatic coronary artery disease Pulmonary: No severe hypoxemia pO2 less than 70 mm Hg
with decreased DLCO less than 70% predicted OR No mild hypoxemia pO2 less than 80 mm Hg
with severely decreased DLCO less than 60% predicted Other: HIV negative Not pregnant or
nursing Fertile patients must use effective contraception during and for one year after
study No leukoencephalopathy

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified
Endocrine therapy: Not specified Radiotherapy: No more than 3,000 cGy prior radiotherapy
to brain No more than 1,500 cGy prior radiotherapy to chest or abdomen Surgery: Not
specified

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Ann E. Woolfrey, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

1457.00

NCT ID:

NCT00005854

Start Date:

December 1999

Completion Date:

October 2000

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • recurrent childhood acute lymphoblastic leukemia
  • refractory multiple myeloma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • recurrent childhood lymphoblastic lymphoma
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • recurrent childhood acute myeloid leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • relapsing chronic myelogenous leukemia
  • refractory chronic lymphocytic leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • meningeal chronic myelogenous leukemia
  • adult acute myeloid leukemia in remission
  • adult acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • childhood acute lymphoblastic leukemia in remission
  • 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
  • secondary acute myeloid leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent childhood large cell lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic 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
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Johns Hopkins Oncology CenterBaltimore, Maryland  21287
University of Massachusetts Memorial Medical CenterWorcester, Massachusetts  01655
University of South Carolina School of MedicineColumbia, South Carolina  29203