Clinical Trial: NCT03019640 - My Cancer Genome

NCT03019640

Description:

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.

Related Conditions:

B-Cell Non-Hodgkin Lymphoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03019640

Trial Eligibility

Document

Title

Brief Title: 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
Official Title: Immunotherapy With Ex Vivo-Expanded Cord Blood-Derived NK Cells Combined With Rituximab High-Dose Chemotherapy and Autologous Stem Cell Transplant for B-Cell Non-Hodgkin's Lymphoma

Clinical Trial IDs

ORG STUDY ID: 2015-0751
SECONDARY ID: NCI-2018-01239
SECONDARY ID: 2015-0751
SECONDARY ID: P30CA016672
NCT ID: NCT03019640

Conditions

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

Interventions

Drug	Synonyms	Arms
Carmustine	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	Treatment (chemotherapy, NK infusion, stem cell transplant)
Cord Blood-derived Expanded Allogeneic Natural Killer Cells	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	Treatment (chemotherapy, NK infusion, stem cell transplant)
Cytarabine	.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	Treatment (chemotherapy, NK infusion, stem cell transplant)
Etoposide	Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16	Treatment (chemotherapy, NK infusion, stem cell transplant)
Filgrastim	G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim	Treatment (chemotherapy, NK infusion, stem cell transplant)
Lenalidomide	CC-5013, CC5013, CDC 501, Revlimid	Treatment (chemotherapy, NK infusion, stem cell transplant)
Melphalan	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	Treatment (chemotherapy, NK infusion, stem cell transplant)
Rituximab	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	Treatment (chemotherapy, NK infusion, stem cell transplant)

Purpose

Detailed Description

      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.

Trial Arms

Name	Type	Description	Interventions
Treatment (chemotherapy, NK infusion, stem cell transplant)	Experimental	See Detailed Description.	Carmustine Cord Blood-derived Expanded Allogeneic Natural Killer Cells Cytarabine Etoposide Filgrastim Lenalidomide Melphalan Rituximab

Eligibility Criteria

        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

Maximum Eligible Age:	70 Years
Minimum Eligible Age:	15 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Treatment-related mortality within 30 days (TRM30)
Time Frame:	Up to 30 days
Safety Issue:
Description:	TRM30 will be estimated using a 95% credible interval assuming a beta(.50, .50) prior.

Secondary Outcome Measures

Measure:	Relapse-free survival (RFS)
Time Frame:	From the time of transplant assessed up to progression or relapse, assessed up to 3 years
Safety Issue:
Description:	Unadjusted RFS will be estimated by the method of Kaplan and Meier.

Measure:	Overall survival (OS)
Time Frame:	From the time of transplant, assessed up to 3 years
Safety Issue:
Description:	Unadjusted OS will be estimated by the method of Kaplan and Meier.

Measure:	Natural killer (NK) cell persistence
Time Frame:	Up to 14 weeks
Safety Issue:
Description:	A Bayesian hierarchical regression model will be fit to the longitudinal NK cell data to assess its patterns over time and association with patient covariates, including type of lymphoma, age, and disease severity.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

August 16, 2021

Clinical Trials /

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