Yttrium Y 90 Basiliximab and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Mature T-cell Non-Hodgkin Lymphoma

NCT02342782 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 14349NCI-2015-00019
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of yttrium Y 90 basiliximab when given together with standard combination chemotherapy before a stem cell transplant in treating patients with mature T-cell non-Hodgkin lymphoma. Radioactive substances linked to monoclonal antibodies, such as yttrium Y 90 basiliximab, can bind to cancer cells and give off radiation which may help kill cancer cells. Drugs used in chemotherapy, such as carmustine, cytarabine, etoposide, and melphalan (BEAM), 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. Giving yttrium Y 90 basiliximab and chemotherapy before a stem cell transplant may help kill any cancer cells that are in the body and help make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Stem cells that were collected from the patient's blood and stored before treatment are later returned to the patient to replace the blood-forming cells that were destroyed.

Conditions

Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• MTD of yttrium Y 90 basiliximab defined as the highest dose in which fewer than 33% of patients experience dose limiting toxicity attributable to study treatment, among those evaluable for toxicity

  Dose limiting toxicities will be graded by the Modified Bearman scale.

  30 days post-transplant

• Incidence of toxicities assessed using National Cancer Institute (NCI) CTCAE version 4.03

  Observed toxicities will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.03 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.

  Up to 100 days post-transplant

Secondary Outcomes (7)

• Disease response by Cheson 2007 criteria

  Up to 2 years post-transplant

• Engraftment: neutrophil and platelet recovery

  Up to 2 years post-transplant

• Overall survival

  From start of therapy (stem cell infusion) to death from any cause, assessed up to 2 years post-transplant

• Progression-free survival

  From start of therapy (stem cell infusion) to the first observation of disease relapse/progression or death from any cause, assessed up to 2 years post-transplant

• Non-relapse mortality

  From start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 2 years post-transplant

Study Arms (1)

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

EXPERIMENTAL

Patients receive yttrium Y 90 basiliximab IV on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV BID on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0.

Biological: Yttrium Y 90 Basiliximab; Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Yttrium Y 90 Basiliximab BIOLOGICAL

Given IV

Also known as: 90Y Basiliximab

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Carmustine DRUG

Given IV

Also known as: FDA 0345, BCNU, BiCNU

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Etoposide DRUG

Given IV

Also known as: Lastet, VP-16

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Cytarabine DRUG

Given IV

Also known as: CHX-3311, U-19920, Ara-C, Cytosar

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Melphalan DRUG

Given IV

Also known as: Alkeran, L-PAM

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo AHCT

Also known as: Autologous Stem Cell Transplantation

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Eligibility Criteria

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

You may qualify if:

• Patients with a pathologically confirmed diagnosis of systemic mature T-cell non-Hodgkin lymphoma (NHL) with City of Hope pathology review as per World Health Organization (WHO) classification of lymphomas 2008, who are deemed eligible for high dose therapy and AHCT including patients in:
• \* T-NHL histologies including peripheral T-cell lymphomas (PTCLs), cutaneous T-cell lymphomas (CTCLs) and natural killer (NK)/T cell lymphomas
• First remission after initial first-line therapy (CR1) in PTCL patients, except for anaplastic lymphoma receptor tyrosine kinase (ALK)+ anaplastic large cell lymphoma (ALCL) and CTCL; patients with minimal residual disease after induction therapy may also be eligible at the discretion of the principal investigator (PI)
• Relapsed/refractory disease, stable disease, partial remission (PR) or complete remission (CR), who have received at least 2 lines of therapy, and do not have an adequate allogenetic stem cell transplant option
• Life expectancy \>= 6 months
• Karnofsky status \>= 70%
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• Cardiac ejection fraction of \>= 50% by echocardiogram or multi gated acquisition scan (MUGA)
• Forced expiratory volume in one second (FEV1) \> 65% of predicted measured, or diffusing capacity of the lung for carbon monoxide (DLCO) \> 50% of predicted measured
• Bilirubin \< 1.5 x normal except in cases where abnormal liver function tests (LFTS) are due to involvement with T-NHL
• Serum glutamic oxaloacetic transaminase (SGOT) AND serum glutamate pyruvate transaminase (SGPT) \< 2 x normal except in cases where abnormal LFTS are due to involvement with T-NHL
• Serum creatinine of \< 1.5 mg/dL, and a measured creatinine clearance of \> 60 mL/min
• Patients will be enrolled at collection of at least 3.0 x 10\^6 CD34 cells/kg of autologous hematopoietic progenitor cells (HPC-A) by apheresis; a minimum of 2 collection procedures is required, unless collection on day # 1 \> 5.0 x 10\^6, CD34 cells/kg; a maximum of 10 collections is allowed; bone marrow harvest to supplement apheresis is not allowed
• Recovery from non-hematologic toxicities of salvage cytoreductive chemotherapy to =\< grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 4 \[v4\])
• Body mass index (BMI) \> 35% will be considered on a case-by-case basis by the Radiation Oncology principal investigator (P.I.)

You may not qualify if:

• Progressive disease
• Patients should not have any uncontrolled illness including ongoing or active infection requiring therapy
• Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy; may have received an experimental agent prior to enrolling in the trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to basiliximab
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with indium In 111 (111In-) and 90Y-basiliximab-DOTA
• Prior high dose chemotherapy for autologous hematopoietic cell transplantation or prior allogeneic transplantation
• Significant prior external beam dose-limiting radiation to a critical organ based on review of the prior radiation treatment records by the Radiation Oncology PI; patients who have had prior external beam radiation \> 2000 cGy (at 180 to 200 cGy per day) to the lung will be ineligible; patients with ANY prior radiation to the heart are ineligible; patients with \> 500 cGy to the kidney will be excluded from the study; Note: patients who have had electron beam therapy are still eligible and will be evaluated on a case by case basis by the Radiation Oncology PI
• Presence of antibody against basiliximab in serum (only required for patients who have received prior antibody)
• Research participants with presence of other active malignancy; however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible; any history of myelodysplasia is excluded
• Active hepatitis B or C viral infection or hepatitis B surface antigen positive
• Patients with a detectable human immunodeficiency virus (HIV) viral load or who are HIV-positive AND have a resistant genotype
• Patients with psychosocial circumstances or illnesses that preclude protocol participation (to be determined by P.I.)
• Any cytogenetic abnormality in the bone marrow that is known to be associated with or predictive of myelodysplasia is excluded; this includes, but is not limited to, del(5), del(7), del(11)
• Evidence of marrow disease by flow and morphology after upfront or salvage cytoreductive therapy and before stem cell mobilization
• Bone marrow (BM) harvest required to reach adequate cell dose for transplant

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

• Zain J, Tsai NC, Palmer J, Simpson J, Adhikarla V, Bading JR, Yazaki P, Smith EP, Dandapani S, Song JY, Karras NA, Herrera AF, Salhotra A, Nademanee AP, Nakamura R, Smith DL, Yamauchi D, Poku EK, Biglang-Awa VE, Colcher D, Shively JE, Wu AM, Forman SJ, Wong J, Thomas S. Yttrium-90 anti-CD25 BEAM conditioning for autologous hematopoietic cell transplantation in Peripheral T-cell lymphoma. Blood Adv. 2024 Sep 24;8(18):4812-4822. doi: 10.1182/bloodadvances.2023012497.

  PMID: 38838232 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous

Interventions

Carmustine; Etoposide; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Jasmine Zain, MD

  City of Hope Medical 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: January 15, 2015
• First Posted: January 21, 2015
• Study Start: June 8, 2020
• Primary Completion: September 18, 2020
• Study Completion: November 18, 2024
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

US (1)