Clinical trial NCT00823524: Donor Natural Killer Cells After Donor Stem Cell Transplant in Treating Patients With Advanced Cancer
Official title: Donor NK Cell Infusion for Progression/Recurrence of Underlying Malignant Disorders After HLA-haploidentical HCT - a Phase 1-2 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Lymphoproliferative Disorder
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: accelerated phase chronic myelogenous leukemia
acute undifferentiated 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)
atypical chronic myeloid leukemia, BCR-ABL1 negative
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
mast cell leukemia
meningeal chronic myelogenous leukemia
progressive hairy cell leukemia, initial treatment
prolymphocytic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
stage III adult T-cell leukemia/lymphoma
stage III chronic lymphocytic leukemia
stage IV adult T-cell leukemia/lymphoma
stage IV chronic lymphocytic leukemia
T-cell large granular lymphocyte leukemia
adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell 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 III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage III mycosis fungoides/Sezary syndrome
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
stage IV mycosis fungoides/Sezary syndrome
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic 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 grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
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
intraocular lymphoma
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma
post-transplant lymphoproliferative disorder
chronic eosinophilic leukemia
chronic neutrophilic leukemia
primary myelofibrosis
essential thrombocythemia
polycythemia vera
extramedullary plasmacytoma
isolated plasmacytoma of bone
stage II multiple myeloma
stage III multiple myeloma
primary systemic amyloidosis
refractory multiple myeloma
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
myelodysplastic/myeloproliferative neoplasm, unclassifiable
cutaneous B-cell non-Hodgkin lymphoma
Waldenström macroglobulinemia
unspecified adult solid tumor, protocol specific
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Korea Research Institute of Bioscience & Biotechnology
First posted: 2009-01-15
Enrollment: 47
Sex: ALL
Minimum age (years): 15
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving an infusion of natural killer cells from a donor after a donor stem cell transplant may help kill any remaining cancer cells after the transplant.

PURPOSE: This phase I/II trial is studying the side effects and best dose of donor natural killer cells when given after a donor stem cell transplant in treating patients with advanced cancer.

Detailed description: OBJECTIVES:

Primary

* To assess the safety of donor natural killer (NK) cell infusion after HLA-mismatched/haploidentical allogeneic hematopoietic stem cell transplantation from a familial donor in patients with advanced malignant disorders.
* To determine the maximum number of donor NK cells that can be safely given to these patients.

Secondary

* To assess the clinical efficacy donor NK cell infusion, in terms of tumor response, response duration, and survival, in patients with progressive or recurrent malignant disorders.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

* Phase I: Patients receive an infusion of donor natural killer (NK) cells on days 18 and 21.
* Phase II: Patients receive an infusion of donor NK cells on days 14 and 21. After completion of study treatment, patients are followed periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of a malignant disorder (hematologic malignancies or solid tumors)

  * Advanced disease
* Has undergone prior allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-mismatched/haploidentical familial donor
* Progressive or recurrent disease, as defined by any of the following (phase II):

  * Peripheral blood blast \> 20% with bone marrow aspirate showing \> 5% leukemic cells (in patients with acute leukemia)
  * Detection of metaphases in the marrow with the same clonal cytogenetic abnormalities as identified before HSCT (or by FISH markers, if appropriate) (in patients with acute leukemia or high-risk myelodysplastic syndromes \[MDS\])
  * Persistent cytopenia with bone marrow aspirate showing various degrees of dysplasia involving ≥ 1 cell lineage (in patients with high-risk MDS)
  * Enlargement of pre-existing measurable lesions by 20% according to RECIST criteria (in patients with solid tumors or lymphoma)
  * Appearance of new metastatic lesions, including pleural effusion or ascites, radiologically typical for metastases or confirmed as such by cytology (in patients with solid tumors or lymphoma)
* Measurable disease (phase II)

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* Total bilirubin \< 3.0 mg/dL
* AST \< 5 times upper limit of normal
* Creatinine \< 3 mg/dL
* Not pregnant or nursing
* No clinically evident cardiac or pulmonary failure

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Safety
timeFrame: 15 days to 1 year after transplantation
Secondary outcomes:
measure: Clinical efficacy of donor NK cell infusion, in terms of tumor response, response duration, and survival
timeFrame: 15 days to 1 year
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: University of Ulsan, Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Kyoo H. Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: