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

Phase I Study of Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Plus Standard BEAM Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Mature T-Cell Non-Hodgkin Lymphoma: the aTAC BEAM Regimen

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Etoposide; Other: Pharmacological Study; Drug: Cytarabine; Drug: Melphalan; Drug: Carmustine; Biological: Yttrium Y 90 Basiliximab; Procedure: Autologous Hematopoietic Stem Cell Transplantation

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if administration of 90Y-basiliximab/DOTA (yttrium Y 90 basiliximab), when given in combination with standard dose BEAM, as conditioning for autologous hematopoietic cell transplant (AHCT), is safe, by evaluation of toxicities, including type, frequency, severity, attribution, time course and duration.

II. To determine the maximum tolerated dose (MTD) of 90Y-basiliximab/DOTA when given in combination with standard dose BEAM, in patients with T-cell non-Hodgkin lymphoma (T-NHL) as part of conditioning for AHCT.

SECONDARY OBJECTIVES:

I. To characterize and evaluate hematologic recovery in terms of neutrophil and platelet engraftment time.

II. To estimate radiation doses to the whole body and normal organs through serial imaging studies.

III. To estimate overall survival, progression-free survival, non-relapse mortality and cumulative incidence of relapse/progression at 100-days (non-relapse mortality [NRM] only), 1-year and 2-years.

OUTLINE: This is a dose-escalation study of yttrium Y 90 basiliximab.

Patients receive yttrium Y 90 basiliximab intravenously (IV) on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV twice daily (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.

After completion of study treatment, patients are followed up at 30, 100, and 180 days and 1, 1.5, and 2 years.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.)
• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Systemic chemotherapy or radiation cannot have been given within 4 weeks prior to the Y-90 dose of radioimmunotherapy (RIT), with the exception of single agent cyclophosphamide priming chemotherapy administered for mobilization

Exclusion Criteria:

• 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
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (yttrium Y 90 basiliximab, BEAM, AHCT); 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Etoposide; Given IV; Other Names: Lastet; VP-16; Other: Pharmacological Study; Correlative studies; Other Names: pharmacological studies; Drug: Cytarabine; Given IV; Other Names: Ara-C; CHX-3311; Cytosar; U-19920; Drug: Melphalan; Given IV; Other Names: Alkeran; L-PAM; Drug: Carmustine; Given IV; Other Names: BCNU; BiCNU; FDA 0345; Biological: Yttrium Y 90 Basiliximab; Given IV; Other Names: 90Y Basiliximab; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo AHCT; Other Names: Autologous Stem Cell Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Survival estimates will be calculated using the Kaplan-Meier method.	From start of therapy (stem cell infusion) to death from any cause, assessed up to 2 years post-transplant
Progression-free survival	Survival estimates will be calculated using the Kaplan-Meier method.	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	The cumulative incidence of relapse/progression and non-relapse mortality will be calculated as competing risks using the Gray method.	From start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 2 years post-transplant
Cumulative incidence of relapse/progression	The cumulative incidence of relapse/progression and non-relapse mortality will be calculated as competing risks using the Gray method.	From start of therapy (stem cell infusion) to the first observation of disease relapse/progression, assessed up to 2 years post-transplant
Absorbed radiation dose to organs assessed by nuclear scan images		Up to day -14

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jasmine Zain, MD, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Actual): September 18, 2020
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (Estimated): January 21, 2015

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Lymphoma; Recurrence; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Melphalan; Cytarabine; Carmustine; Basiliximab
• Other Study ID Numbers: 14349 (Other Identifier: City of Hope Medical Center); NCI-2015-00019 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No