Clinical trial NCT00265837: Laboratory-Treated Donor Bone Marrow in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer
Official title: Phase III Trial of T Lymphocyte Depletion by Elutriation and CD34 Add-Back for Allogeneic Bone Marrow Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Keywords: graft versus host disease
adult acute myeloid leukemia in remission
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)
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
childhood acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
childhood acute lymphoblastic leukemia in remission
recurrent childhood acute lymphoblastic leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
chronic myelomonocytic leukemia
juvenile myelomonocytic leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
Philadelphia chromosome negative chronic myelogenous leukemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent adult 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/refractory childhood Hodgkin lymphoma
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell 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
splenic marginal zone lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult immunoblastic large cell lymphoma
childhood myelodysplastic syndromes
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-12-15
Enrollment: 72
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy and total-body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening.

PURPOSE: This randomized phase III trial is studying donor bone marrow that is treated in the laboratory using two different devices to compare how well they work in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.

Detailed description: OBJECTIVES:

* Compare the effectiveness, in terms of incidence of graft failure and incidence of greater than grade 1 acute graft-vs-host disease, of ex vivo manipulation of bone marrow cells comprising counterflow centrifugal elutriation for T-lymphocyte depletion followed by CD34-positive stem cell selection using CliniMACS vs Isolex 300i in patients with a hematologic malignancy undergoing allogeneic bone marrow transplantation from an HLA-identical sibling donor.

OUTLINE: This is a randomized study. Patients are stratified by age (\< 40 vs 40-65) and disease status (low-risk \[i.e., chronic phase chronic myelogenous leukemia, acute myeloid leukemia in first complete remission (CR), acute lymphocytic leukemia in first CR, Hodgkin's or non-Hodgkin's lymphoma in sensitive relapse, or multiple myeloma in CR or partial remission) vs high-risk \[i.e., all others\]). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Allogeneic bone marrow cells are subjected to counterflow centrifugal elutriation (CCE) for T-lymphocyte depletion. The elutriation fractions are then processed over 2-2.5 hours using CliniMACS to select for CD34-positive stem cells.
* Arm II: Allogeneic bone marrow cells are subjected to CCE for T-lymphocyte depletion. The elutriation fractions are then processed over 4-4.5 hours using Isolex 300i to select for CD34-positive stem cells.

Patients in both arms then undergo ex vivo manipulated, T-lymphocyte-depleted, CD34-positive stem cell-selected, allogeneic bone marrow transplantation on day 0.

After the transplantation, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 206 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following hematologic malignancies or genetic disorders:

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

    * Primary resistant disease
    * Disease in complete remission (CR)
    * Disease in first early relapse
    * Secondary AML arising out of myelodysplastic syndrome
  * Acute lymphocytic leukemia (ALL), meeting 1 of the following criteria:

    * Primary resistant disease
    * Disease in CR
    * Disease in first early relapse
  * Chronic myelogenous leukemia
  * Myelodysplastic syndrome (MDS)
  * Chronic myelomonocytic leukemia
  * Philadelphia chromosome-negative myeloproliferative disorder
  * Multiple myeloma
  * Hodgkin's lymphoma
  * Non-Hodgkin's lymphoma
  * Genetic disorders or inborn errors of metabolism
* Planning allogeneic bone marrow transplantation at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Medical Center

  * Must have an HLA-identical sibling donor by serologic or molecular typing of HLA class I antigens and molecular typing of HLA class II antigens

PATIENT CHARACTERISTICS:

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior red blood cell or platelet transfusion from the same donor

Other

* Concurrent participation in another clinical trial allowed

Primary outcomes:
measure: Incidence of graft-vs-host disease or graft failure
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Richard J. Jones, MD
role: PRINCIPAL_INVESTIGATOR
References: