NCT00625729 · REGISTRY CONDITION SEARCH

Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: TERMINATED
Registry last update: 2017-12-28

RATIONALE: Aldesleukin may stimulate natural killer cells to kill cancer cells. Treating natural killer cells with aldesleukin in the laboratory may help the natural killer cells kill more cancer cells when they are put back in the body. Giving monoclonal antibodies, such as rituximab, and chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor natural killer cell infusion helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. PURPOSE: This phase I/II trial is studying how well giving rituximab and chemotherapy followed by a donor natural killer cell infusion that has been treated in the laboratory with aldesleukin followed by aldesleukin works in treating patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Number of Patients Exhibiting Natural Killer Cell Expansion

→

outcome · POSTED

Number of Patients With Interleukin-15 Production and NK Cell Expansion

→

outcome · POSTED

Number of Patients With Overall Response

→

outcome · POSTED

Number of Patients Whose Disease Progressed After Treatment

→

outcome · POSTED

Number of Patients With Adequate Natural Killer Cells Infused

→

outcome · POSTED

Number of Patients With Overall Survival

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: * Patient 18 years or older with a diagnosis of non-Hodgkin Lymphoma or chronic lymphocytic leukemia (NHL or CLL) and one of the following: * Progression of NHL following at least 2 prior chemotherapy regimens, (must contain rituximab for all NHL and fludarabine for follicular NHL) defined as: * failure to achieve partial remission (PR) with the last chemotherapy * disease progression within 6 months following last chemotherapy * Progression of CLL/SLL (small lymphocytic lymphoma) following at least 2 prior chemotherapy regimens (containing purine analogs ) in stage Rai III or IV or symptomatic disease. * Relapsed NHL or CLL following stem cell transplantation for whom the option of donor lymphocyte infusion is not available or clinically indicated (e.g. recipients of autologous or umbilical cord blood \[UCB\] transplants). * Available related HLA-haploidentical (human leukocyte antigen) natural killer (NK) cell adult donor by at least Class I serologic typing * Karnofsky performance status \> 60% * Measurable disease based on modified Response Evaluation Criteria In Solid Tumors (RECIST) * Have acceptable organ function as defined within 28 days of enrollment: * Hematologic: platelets ≥ 80,000 x 10\^9/L; hemoglobin ≥ 9g/dL, unsupported by transfusions; absolute neutrophil count (ANC) ≥ 1000 x 10\^9/L, unsupported by granulocyte-colony stimulating factor or granulocyte-macrophage colony-stimulating factor (G-CSF or GM-CS)F for 10 days or Neulasta for 21 days - the hematologic requirements are waived for patients with inadequate counts due to known bone marrow involvement by lymphoma who are otherwise eligible * Renal: glomerular filtration rate (GFR) \> 50 ml/min * Hepatic: alanine aminotransferase (ALT), aspartate aminotransferase (AST) \< 3 x upper limit of normal and total bilirubin \<3 mg/dl * Pulmonary function: \>50% corrected carbon monoxide diffusing capacity (DLCO) and Forced Expiratory Volume in the first second (FEV1) * Cardiac: no symptoms of uncontrolled cardiac disease, left ventricular ejection fraction \>40% * Off prednisone or other immunosuppressive medications for at least 3 days prior to Day 0 * Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment. * Voluntary written informed consent before performance of any study-related procedure not part of normal medical care. Exclusion Criteria: * Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. Women of childbearing age must use appropriate contraceptive method. * Active central nervous system (CNS) lymphoma/leukemia * Active serious infection (pulmonary infiltrates or lesions are allowed only after the appropriate diagnostic testing is negative for infection or appropriate therapy was initiated for probable infection) * Pleural effusion - large enough to be detectable on the chest x-ray * Allergy to rituximab or IL-2 * Human immunodeficiency virus (HIV) and associated non-Hodgkins lymphoma (NHL) * Active concurrent malignancy (except skin cancer) requiring systemic therapy in the past 2 years * Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder * Positive hepatitis B surface antigen (HBsAg). If Hepatitis B core antibody (HBcAb) is positive, Hepatitis B deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) will be evaluated. Positive anti HBcAb and undetectable viral load does not exclude the patient. * Any experimental therapy in the past 30 days Donor Selection: * Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling) ≥ age 18 years * Able and willing to undergo lymphapheresis * HLA-haploidentical donor/recipient match. If time permits and multiple donors are available, preference will be given to the Killer-cell Immunoglobulin-like Receptors (KIR) ligand mismatched donor (as predicted by HLA typing). * HIV-1, HIV-2 negative, Human T-lymphotropic virus Type I (HTLV-1), HTLV-2 negative, West Nile virus (WNV) negative, Hepatitis B and C negative * Adequate organ function defined as: * Hematologic: CBC/diff/platelet count near normal limits, * Hepatic: ALT \< 2 x upper limit of normal, * Not pregnant or lactating * In general good health as determined by the study physician * Able to give informed consent
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with donor natural killer cells infusion, rituximab, aldesleukin and chemotherapy.
intervention Names
Biological: aldesleukin
Biological: allogeneic natural killer cells
Biological: rituximab
Drug: cyclophosphamide
Drug: fludarabine phosphate
label
Treated Patients
type
EXPERIMENTAL

interventions

arm Group Labels
Treated Patients
description
Day 0-14, 10 million international units, 3 times per week for 6 doses
name
aldesleukin
other Names
IL-2
type
BIOLOGICAL
arm Group Labels
Treated Patients
description
Day 0 infusion of cells (1.5-8 x 10\^7 cells/kg).
name
allogeneic natural killer cells
other Names
Natural Killer Cells
type
BIOLOGICAL
arm Group Labels
Treated Patients
description
Administered Day -8, day -1, day +6 and day +13, intravenously (IV) 357 mg/m\^2
name
rituximab
other Names
Rituxan
type
BIOLOGICAL
arm Group Labels
Treated Patients
description
60 mg/kg intravenous (IV) on Day -5.
name
cyclophosphamide
other Names
Cytoxan
type
DRUG
arm Group Labels
Treated Patients
description
Day -6 through day -2, 25 mg/m\^2 intravenous (IV)
name
fludarabine phosphate
other Names
Fludara
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 6
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Successful natural killer (NK) cell expansion will be defined as an absolute circulating donor-derived NK cell count of \>100 cells/μl 14 days after infusion with \<5% donor T and B cells in the mononuclear population.
measure
Number of Patients Exhibiting Natural Killer Cell Expansion
time Frame
Day 14

secondary Outcomes

description
Correlation of interleukin-15 production at day 0 with natural killer (NK) cells expansion
measure
Number of Patients With Interleukin-15 Production and NK Cell Expansion
time Frame
Day 0
description
Overall response (complete remission plus partial remission) rate at 3 months, as defined by International Working Group for non-Hodgkin lymphoma and NCI Working Group guidelines for chronic lymphocytic leukemia
measure
Number of Patients With Overall Response
time Frame
3 Months
description
Includes patients (with non-Hodgkin leukemia or chronic lymphocytic leukemia) whose disease progressed after treatment.
measure
Number of Patients Whose Disease Progressed After Treatment
time Frame
6 Months
description
Incidence of donor products that met release criteria in accordance with FDA regulations (Lot Release Criteria for allogeneic, interleukin-2 (IL-2) activated natural killer (NK) cell products (BB-IND 8847) and the NK cell numbers infused (donor NK cell dose 1.5-8.0 x 10\^7/kg).
measure
Number of Patients With Adequate Natural Killer Cells Infused
time Frame
Day 0
description
Number of patients alive at 6 months after treatment.
measure
Number of Patients With Overall Survival
time Frame
6 Months

Full study description

brief Summary: RATIONALE: Aldesleukin may stimulate natural killer cells to kill cancer cells. Treating natural killer cells with aldesleukin in the laboratory may help the natural killer cells kill more cancer cells when they are put back in the body. Giving monoclonal antibodies, such as rituximab, and chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor natural killer cell infusion helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. PURPOSE: This phase I/II trial is studying how well giving rituximab and chemotherapy followed by a donor natural killer cell infusion that has been treated in the laboratory with aldesleukin followed by aldesleukin works in treating patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia.
detailed Description: OBJECTIVES: Primary * To determine if allogeneic natural killer (NK) cells infused following chemoimmunotherapy can be safely expanded in vivo with aldesleukin. Secondary * To determine if interleukin-15 production at day 0 correlates with NK cells expansion. * To determine overall response rate at 3 months. * To determine time to progression and overall survival. * To characterize the quantitative and qualitative toxicities of this treatment plan. * To determine the incidence of donor products that do not meet release criteria and the NK cell numbers infused. * To correlate clinical response with donor/recipient KIR ligand matching status, FcG receptor 3A genotype, and NK cells phenotype and function * To determine pharmacodynamic and pharmacogenomic markers and correlate them with NK cell expansion and disease response. OUTLINE: * Conditioning regimen: Patients receive rituximab intravenously (IV) over 6-8 hours on days -8, -1, 6, and 13; fludarabine IV on days -6 to -2; and cyclophosphamide IV on day -5. * Allogeneic natural killer (NK) cell administration: Patients receive aldesleukin-activated haploidentical NK cells IV over less than 1 hour on day 0. Within 4 hours after allogeneic NK cell infusion, patients receive aldesleukin subcutaneously (SC) 3 times a week for 6 doses. Patients also receive filgrastim (G-CSF) SC beginning on day 14 and continuing until absolute neutrophil count (ANC) is \> 2,500/mm³ for 2 consecutive days. Patients who achieve a complete or partial response at 28 days are eligible for allogeneic stem cell transplantation. Patients who achieve initial response at 3 months, clinically benefit from treatment, but subsequently relapse are eligible for retreatment provided all eligibility criteria are met. Blood samples are collected periodically for correlative laboratory studies. Patients with chronic lymphocytic leukemia (CLL) also undergo bone marrow aspiration periodically for correlative laboratory studies. After completion of study treatment, patients are followed periodically for up to 1 year.

Source references

Source notices and limitations

Discovery and provenance

release id
ctgov-registry-1336d216cbd1bbff780dac70
edge id
nct-edge-aa2664264c846ef722a0
requested nct id
NCT00625729
primary nct id
NCT00625729
source kind
ctgov_condition_query
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true
source record id
Source null
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
payload sha256
f08f55a932bf0293b10ba34711fda7a8e725968672a29663295eba2c2b9b3b4c
payload
clinical indication matching status
condition_index_match_asserted_by_registry_not_reviewed
end exclusive
true
id
nct-edge-aa2664264c846ef722a0
link basis
returned_by_explicit_condition_and_posted_results_filter_query
nct id
NCT00625729
occurrences
context exact
NCT00625729
end
11
exact text
NCT00625729
start
0
offset unit
unicode_code_points
query cond
Plasma Cell Neoplasms
query disease state id
ds-plasma-cell-neoplasms
source file
/Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-plasma-cell-neoplasms-000.json
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
source json pointer
/studies/937/protocolSection/identificationModule/nctId
source kind
ctgov_condition_query
source record id
Source null
source string basis
parsed_JSON_string_unmodified
source string sha256
1a24473d8b6ff775c4b6d32e234ad02eed1fa8a9ca07f8d1b4667ded6de77a5b
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true

Preserved source evidence · Not medical advice