Umbilical Cord Blood NK Cells, Rituximab, High-Dose Chemotherapy, and Stem Cell Transplant in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma

NCT ID: NCT03019640

Last Updated: 2023-02-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-10

Study Completion Date

2021-08-16

Brief Summary

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This phase II trial studies the side effects of cord blood-derived expanded allogeneic natural killer cells (umbilical cord blood natural killer \[NK\] cells), rituximab, high-dose chemotherapy, and stem cell transplant in treating patients with B-cell non-Hodgkin's lymphoma that has come back (recurrent) or that does not respond to treatment (refractory). Immune system cells, such as cord blood-derived expanded allogeneic natural killer cells, are made by the body to attack foreign or cancerous cells. Immunotherapy with rituximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carmustine, cytarabine, etoposide, lenalidomide, melphalan, and rituximab, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. A stem cell transplant using stem cells from the patient or a donor may be able to replace blood-forming cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Giving cord blood-derived expanded allogeneic natural killer cells, rituximab, high-dose chemotherapy, and stem cell transplant may work better in treating patients with recurrent or refractory B-cell non-Hodgkin's lymphoma.

Detailed Description

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PRIMARY OBJECTIVE:

I. To establish the safety of this treatment by determining its treatment-related mortality (TRM) within 30 days.

SECONDARY OBJECTIVES:

I. To estimate the relapse-free survival (RFS). II. To estimate the overall survival (OS). III. To quantify duration of infused allogeneic umbilical cord blood (UCB)-derived natural killer (NK) cells in the recipient.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive carmustine intravenously (IV) over 2 hours on day -12, etoposide IV twice daily (BID) over 3 hours on days -11 to -8, cytarabine IV BID over 1 hour on days -11 to -8, melphalan IV over 30 minutes on day -7, and lenalidomide orally (PO) once daily (QD) on days -7 to -2 in the absence of disease progression or unacceptable toxicity. Patients who are CD20+ also receive rituximab IV over 3 hours on days -13 and -7.

NK-CELL INFUSION: Patients receive cord blood-derived expanded allogeneic NK cells IV over 1 hour on day -5 in the absence of disease progression or unacceptable toxicity.

STEM CELL TRANSPLANT: Patients undergo stem cell transplant IV over 30-60 minutes on day 0 in the absence of disease progression or unacceptable toxicity.

POST-TRANSPLANT: Patients receive filgrastim subcutaneously (SC) QD beginning on day +5. Treatment continues until white blood cell count recovers in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 100, and 180 days.

Conditions

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Mantle Cell Lymphoma Recurrent Diffuse Large B-Cell Lymphoma Recurrent Follicular Lymphoma Recurrent Indolent Adult Non-Hodgkin Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Indolent Adult Non-Hodgkin Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (chemotherapy, NK infusion, stem cell transplant)

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Group Type EXPERIMENTAL

Autologous Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo stem cell transplant

Carmustine

Intervention Type DRUG

Given IV

Cord Blood-derived Expanded Allogeneic Natural Killer Cells

Intervention Type BIOLOGICAL

Given IV

Cytarabine

Intervention Type DRUG

Given IV

Etoposide

Intervention Type DRUG

Given IV

Filgrastim

Intervention Type BIOLOGICAL

Given SC

Lenalidomide

Intervention Type DRUG

Given PO

Melphalan

Intervention Type DRUG

Given IV

Rituximab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Autologous Hematopoietic Stem Cell Transplantation

Undergo stem cell transplant

Intervention Type PROCEDURE

Carmustine

Given IV

Intervention Type DRUG

Cord Blood-derived Expanded Allogeneic Natural Killer Cells

Given IV

Intervention Type BIOLOGICAL

Cytarabine

Given IV

Intervention Type DRUG

Etoposide

Given IV

Intervention Type DRUG

Filgrastim

Given SC

Intervention Type BIOLOGICAL

Lenalidomide

Given PO

Intervention Type DRUG

Melphalan

Given IV

Intervention Type DRUG

Rituximab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Autologous Hematopoietic Cell Transplantation autologous stem cell transplantation BCNU Becenum Becenun BiCNU Bis(chloroethyl) Nitrosourea Bis-Chloronitrosourea Carmubris Carmustin Carmustinum FDA 0345 N,N''-Bis(2-chloroethyl)-N-nitrosourea Nitrourean Nitrumon SK 27702 SRI 1720 WR-139021 Allogeneic CB-derived Ex vivo-expanded NK Cells CB-derived Expanded Allogeneic NK Cells UCB-derived Expanded Allogeneic NK Cells Umbilical Cord Blood-derived Expanded Allogeneic Natural Killer Cells .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tevagrastim CC-5013 CC5013 CDC 501 Revlimid Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalanum Phenylalanine Mustard Phenylalanine nitrogen mustard Sarcoclorin Sarkolysin WR-19813 ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab ABBS Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar JHL1101 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 rituximab biosimilar TQB2303 rituximab-abbs RTXM83 Truxima

Eligibility Criteria

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Inclusion Criteria

* Patients with B-cell lymphoma who are candidates to autologous stem-cell transplantation:

* Primary refractory or relapsed diffuse large B-cell lymphoma in response to salvage treatment
* Primary refractory or relapsed follicular lymphoma or other indolent B-cell histology in response to salvage treatment
* Chemosensitive mantle-cell lymphoma in first or later line of treatment
* Estimated serum creatinine clearance \>= 60 ml/min and a normal serum creatinine for age
* Serum glutamic-oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) =\< 3 x upper limit of normal (ULN)
* Total bilirubin and alkaline phosphatase (ALP) =\< 2 x ULN or =\< 3 x ULN for Gilbert's disease
* Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion lung capacity (DLCO) (corrected for hemoglobin \[Hgb\]) \>= 50% of the predicted value
* Left ventricular ejection fraction \>= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease
* Performance status \< 2 (Eastern Cooperative Oncology Group \[ECOG\])
* Negative beta human chorionic gonadotropin (HCG) in woman with child-bearing potential

Exclusion Criteria

* Primary central nervous system (CNS) lymphoma
* Grade \>= 3 non-hematologic toxicity from prior therapy that has not resolved to =\< grade (G) 1
* Prior whole brain irradiation
* Active hepatitis B, either active carrier (hepatitis B surface antigen positive \[HBsAg +\]) or viremic (hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\] \>= 10,000 copies/mL, or \>= 2,000 IU/mL)
* Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
* Active infection requiring parenteral antibiotics
* Human immunodeficiency virus (HIV) infection
* Radiation therapy in the month prior to enroll
* Breastfeeding females
Minimum Eligible Age

15 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yago L Nieto

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.mdanderson.org

MD Anderson Cancer Center Website

Other Identifiers

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NCI-2018-01239

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015-0751

Identifier Type: OTHER

Identifier Source: secondary_id

2015-0751

Identifier Type: -

Identifier Source: org_study_id

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