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

NCT00625729 | Terminated Phase 1 Results DMC

• 4 other identifiers: 2007LS064MT2007-12UMN-0707M13561P01CA065493
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Lymphoma

Keywords

recurrent adult grade III lymphomatoid granulomatosis; adult nasal type extranodal NK/T-cell lymphoma; Waldenstrom macroglobulinemia; 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 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; refractory chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Patients Exhibiting Natural Killer Cell Expansion

  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.

  Day 14

Secondary Outcomes (5)

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

  Day 0

• Number of Patients With Overall Response

  3 Months

• Number of Patients Whose Disease Progressed After Treatment

  6 Months

• Number of Patients With Adequate Natural Killer Cells Infused

  Day 0

• Number of Patients With Overall Survival

  6 Months

Study Arms (1)

Treated Patients

EXPERIMENTAL

Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with donor natural killer cells infusion, rituximab, aldesleukin and chemotherapy.

Biological: aldesleukin; Biological: allogeneic natural killer cells; Biological: rituximab; Drug: cyclophosphamide; Drug: fludarabine phosphate

Interventions

aldesleukin BIOLOGICAL

Day 0-14, 10 million international units, 3 times per week for 6 doses

Also known as: IL-2

Treated Patients

allogeneic natural killer cells BIOLOGICAL

Day 0 infusion of cells (1.5-8 x 10\^7 cells/kg).

Also known as: Natural Killer Cells

Treated Patients

rituximab BIOLOGICAL

Administered Day -8, day -1, day +6 and day +13, intravenously (IV) 357 mg/m\^2

Also known as: Rituxan

Treated Patients

cyclophosphamide DRUG

60 mg/kg intravenous (IV) on Day -5.

Also known as: Cytoxan

Treated Patients

fludarabine phosphate DRUG

Day -6 through day -2, 25 mg/m\^2 intravenous (IV)

Also known as: Fludara

Treated Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Lymphoma, Extranodal NK-T-Cell; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

aldesleukin; Interleukin-2; IL32 protein, human; Rituximab; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Study was terminated early due to lack of NK expansion and failure to meet primary outcome.

Results Point of Contact

• Title: Veronika Bachanova, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

bach0173@umn.edu

612-625-5469

Study Officials

• Veronika Bachanova, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2008
• First Posted: February 28, 2008
• Study Start: January 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: April 1, 2010
• Last Updated: December 28, 2017
• Results First Posted: July 30, 2010

Record last verified: 2017-12

Locations

US (1)