TCR Genetically Engineered PBMC and PBSC After Melphalan Conditioning Regimen in Treating Participants With Relapsed and Refractory Multiple Myeloma

NCT03506802 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 17-001866NCI-2018-00204
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of NY-ESO-1 TCR engineered peripheral blood mononuclear cells (PBMC) and peripheral blood stem cells (PBSC) after melphalan conditioning regimen in treating participants with multiple myeloma that has come back or does not respond to treatment. The melphalan conditioning chemotherapy makes room in the patient?s bone marrow for new blood cells (PBMC) and blood-forming cells (stem cells) to grow. Giving NY-ESO-1 TCR PBMC and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer. Giving NY-ESO-1 TCR PBMC and PBSC after melphalan may work better at treating multiple myeloma.

Conditions

HLA-A*0201 Positive Cells Present; NY-ESO-1 Positive Tumor Cells Present; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting toxicity

  Safety will be assessed by monitoring and recording potential adverse effects of the treatment using the Common Toxicity Criteria at each study visit. Subjects will be monitored by medical histories, physical examinations and blood studies to detect potential toxicities from the treatment. If there are no dose limiting toxicities observed, the cohort will be expanded to 12 subjects. If 1/3 are observed, up to 6 subjects will be recruited. If less than 2/6 are observed, the cohort will be expanded to a total of 12 subjects. If a dose limiting toxicity is observed in 2 or more of 6 subjects, then this dose level will have exceeded the 33% rate, and the study will be terminated.

  Up to 90 days

Secondary Outcomes (11)

• Feasibility of NY-ESO-1 TCR transgenic cells

  Up to 1 month after transgenic cell adoptive transfer

• Persistence of transduced T cells

  Up to 2 years after transgenic cell adoptive transfer

• Engraftment and persistence of transduced progeny T cells

  Up to 2 years after transgenic cell adoptive transfer

• Engraftment and persistence of transduced T cells and progeny T cells

  Up to 2 years after transgenic cell adoptive transfer

• Persistence of TCR gene transduced cells

  Up to 15 years

Other Outcomes (1)

• LV-NYESO TCR/sr39TK peripheral blood stem cell (PBSC) biodistribution (Regional uptake of 18F-FHBG within metastatic tumor sites and secondary lymphoid organs)

  Day 30 and day 90

Study Arms (1)

Treatment (Genetically engineered PBMC and PBSC)

EXPERIMENTAL

Refer to outline

Radiation: 18F-FHBG; Biological: Aldesleukin; Biological: Cellular Therapy; Procedure: Computed Tomography; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Procedure: Leukapheresis; Drug: Melphalan; Drug: Plerixafor; Procedure: Positron Emission Tomography

Interventions

18F-FHBG RADIATION

Given IV

Also known as: Reporter Probe 18F-FHBG

Treatment (Genetically engineered PBMC and PBSC)

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (Genetically engineered PBMC and PBSC)

Cellular Therapy BIOLOGICAL

LV-NYESO TCR /sr39TK PBSC and RV-NYESO TCR PBMC given IV

Also known as: Cell Therapy

Treatment (Genetically engineered PBMC and PBSC)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computerized Axial Tomography, computerized tomography, CT, CT SCAN, tomography

Treatment (Genetically engineered PBMC and PBSC)

Filgrastim BIOLOGICAL

Given SC

Also known as: FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Treatment (Genetically engineered PBMC and PBSC)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Genetically engineered PBMC and PBSC)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (Genetically engineered PBMC and PBSC)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (Genetically engineered PBMC and PBSC)

Melphalan DRUG

Given IV

Also known as: 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 (Genetically engineered PBMC and PBSC)

Plerixafor DRUG

Given SC

Also known as: AMD 3100, JM-3100, Mozobil, SDZ SID 791

Treatment (Genetically engineered PBMC and PBSC)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Treatment (Genetically engineered PBMC and PBSC)

Eligibility Criteria

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

You may qualify if:

• Relapsed, relapsed and refractory or refractory multiple myeloma patients who have received \> 3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD28 monoclonal antibody
• NY-ESO-1 positive by immunohistochemistry (IHC) utilizing commercially available NY-ESO-1 antibodies
• HLA-A\*0201 (HLA-A2.1) positivity by molecular subtyping
• Measurable disease defined by at least one of the following:
• Serum monoclonal protein (serum protein electrophoresis \[SPEP\]) \> 1gm/dL
• Serum free light chain (sFLC): involved free light chain (FLC) \>= 10mg/dL AND abnormal kappa to lambda serum free light chain ratio
• \>= 200mg of monoclonal protein in the urine on 24 hour electrophoresis (urine protein electrophoresis \[UPEP\])
• Adequate bone marrow and major organ function to undergo a PBSC transplant determined within 30-60 days prior to enrollment using standard phase 1 criteria for organ function defined as:
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 cells/L
• Platelets \>= 75 x 10\^9/L
• Hemoglobin \>= 8 g/dL
• Aspartate and alanine aminotransferases (AST, ALT) =\< 2.5 x upper limit of normal (ULN) (=\< 5 x ULN, if documented liver metastases are present)
• Total bilirubin =\< 2 x ULN (except patients with documented Gilbert?s syndrome)
• Creatinine \< 2 mg/dl (or a glomerular filtration rate \> 60)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

You may not qualify if:

• Inability to purify \>= 2.5 x 10\^6 CD34-enriched cells/kg of patient weight from the pooled granulocyte-colony stimulating factor (G-CSF) mobilized leukapheresis products
• Previous allogeneic transplant
• Previously known hypersensitivity to any of the agents used in this study; known sensitivity to melphalan
• Received systemic treatment for multiple myeloma, including immunotherapy, within 14 days prior to initiation of study procedures
• Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
• Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
• Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
• Pregnancy or breast-feeding; female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and for 6 months afterwards; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 14 days from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators
• Since IL-2 is administered following cell infusion:
• Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia with evidence of ischemia on a cardiac stress test (stress thallium, stress multigated acquisition \[MUGA\], dobutamine echocardiogram or other stress test)
• Similarly, patients with a baseline left ventricular ejection fraction (LVEF) \< 45 percent (%) will be excluded
• Patients with ECG results of any conduction delays (PR interval \> 200 ms, corrected QT \[QTC\] \> 480 ms), sinus bradycardia (resting heart rate \< 50 beats per minute), sinus tachycardia (heart rate \> 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as \> 20 premature ventricular contractions \[PVCs\] per minute), ventricular tachycardia or 3rd degree heart block will be excluded from the study unless cleared by a cardiologist
• Patients with pulmonary function test abnormalities as evidenced by a forced expiratory volume in 1 (FEV1) / forced vital capacity (FVC) \< 70% of predicted for normality will be excluded
• Active or recent herpes simplex virus (HSV) infection or cytomegalovirus (CMV) based on symptoms with positive swab culture and/or positive Immunoglobulin M (IgM) screening, which would complicate the post-conditioning period

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

9-(4-fluoro-3-hydroxymethylbutyl)guanine; aldesleukin; Cell- and Tissue-Based Therapy; Filgrastim; Granulocyte Colony-Stimulating Factor; Lenalidomide; Leukapheresis; Melphalan; plerixafor; ferric pyrophosphate; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Sarah Larson, M.D.

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

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: April 13, 2018
• First Posted: April 24, 2018
• Study Start: July 10, 2018
• Primary Completion: June 25, 2019
• Study Completion: June 25, 2019
• Last Updated: July 24, 2020

Record last verified: 2019-06

Locations

US (1)