Clinical Trials /

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

NCT02342782

Description:

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.

Related Conditions:
  • T-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 14349
  • SECONDARY ID: NCI-2015-00019
  • SECONDARY ID: 14349
  • NCT ID: NCT02342782

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

Interventions

DrugSynonymsArms
Yttrium Y 90 Basiliximab90Y BasiliximabTreatment (yttrium Y 90 basiliximab, BEAM, AHCT)
CarmustineFDA 0345, BCNU, BiCNUTreatment (yttrium Y 90 basiliximab, BEAM, AHCT)
EtoposideLastet, VP-16Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)
CytarabineCHX-3311, U-19920, Ara-C, CytosarTreatment (yttrium Y 90 basiliximab, BEAM, AHCT)
MelphalanAlkeran, L-PAMTreatment (yttrium Y 90 basiliximab, BEAM, AHCT)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (yttrium Y 90 basiliximab, BEAM, AHCT)ExperimentalPatients 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.
  • Yttrium Y 90 Basiliximab
  • Carmustine
  • Etoposide
  • Cytarabine
  • Melphalan

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Time Frame:30 days post-transplant
Safety Issue:
Description:Dose limiting toxicities will be graded by the Modified Bearman scale.

Secondary Outcome Measures

Measure:Disease response by Cheson 2007 criteria
Time Frame:Up to 2 years post-transplant
Safety Issue:
Description:
Measure:Engraftment: neutrophil and platelet recovery
Time Frame:Up to 2 years post-transplant
Safety Issue:
Description:
Measure:Overall survival
Time Frame:From start of therapy (stem cell infusion) to death from any cause, assessed up to 2 years post-transplant
Safety Issue:
Description:Survival estimates will be calculated using the Kaplan-Meier method.
Measure:Progression-free survival
Time Frame: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
Safety Issue:
Description:Survival estimates will be calculated using the Kaplan-Meier method.
Measure:Non-relapse mortality
Time Frame:From start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 2 years post-transplant
Safety Issue:
Description:The cumulative incidence of relapse/progression and non-relapse mortality will be calculated as competing risks using the Gray method.
Measure:Cumulative incidence of relapse/progression
Time Frame:From start of therapy (stem cell infusion) to the first observation of disease relapse/progression, assessed up to 2 years post-transplant
Safety Issue:
Description:The cumulative incidence of relapse/progression and non-relapse mortality will be calculated as competing risks using the Gray method.
Measure:Absorbed radiation dose to organs assessed by nuclear scan images
Time Frame:Up to day -14
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

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