Clinical Trial: NCT04871607 - My Cancer Genome

NCT04871607

Description:

This phase II trials studies the effects of yttrium-90 labeled anti-CD25 monoclonal antibody combined with BEAM chemotherapy conditioning in treating patients with Hodgkin lymphoma that does not response to treatment (refractory) or has come back (relapsed). Yttrium-90-labeled anti-CD25 is an antibody (proteins made by the immune system to fight infections) that is attached to a radioactive substance and may kill cancer cells and shrink tumors. Chemotherapy drugs, such as carmustine, etoposide, cytarabine, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow.

Related Conditions:

Hodgkin Lymphoma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04871607

Trial Eligibility

Document

Title

Brief Title: Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Combined With BEAM Chemotherapy Conditioning for the Treatment of Primary Refractory or Relapsed Hodgkin Lymphoma
Official Title: A Phase 2 Trial of Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Combined With BEAM Chemotherapy (aTac-BEAM) Conditioning for Autologous Hematopoietic Cell Transplantation (AHCT) in Patients With Primary Refractory or Relapsed Hodgkin Lymphoma

Clinical Trial IDs

ORG STUDY ID: 20420
SECONDARY ID: NCI-2021-03073
SECONDARY ID: 20420
SECONDARY ID: P30CA033572
NCT ID: NCT04871607

Conditions

Recurrent Hodgkin Lymphoma
Refractory Hodgkin Lymphoma

Interventions

Drug	Synonyms	Arms
Basiliximab	SDZ-CHI-621, Simulect	Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A)
Carmustine	BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, N,N''-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, SK 27702, SRI 1720, WR-139021	Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A)
Cytarabine	.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453	Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A)
Etoposide	Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16	Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A)

Purpose

Detailed Description

      PRIMARY OBJECTIVE:

      I. Evaluate the anti-lymphoma activity of the aTac-carmustine (BCNU), etoposide, cytarabine
      (cytosine arabinoside), and melphalan (BEAM) regimen as conditioning for Autologous
      hematopoietic cell transplantation (AHCT); assessed by 2-year progression-free survival
      (PFS).

      SECONDARY OBJECTIVES:

      I. Estimate the overall survival (OS) probability and cumulative incidence of
      relapse/progression, and non-relapse mortality (NRM) at 100-days, 1-year and 2-years.

      II. Summarize toxicities by type, frequency, severity, attribution, time course and duration.

      III. Evaluate short and long-term complications, including: delayed engraftment (neutrophil
      and platelet), infection, and myelodysplasia (MDS).

      EXPLORATORY OBJECTIVES:

      I. Evaluate potential changes in Hodgkin lymphoma biological markers of patients treated with
      90Y basiliximab BEAM via analyses of serial blood samples.

      II. Assess the potential association between pre-AHCT CD25 expression levels and post-AHCT
      outcomes.

      OUTLINE:

      Patients receive 'cold' basiliximab intravenously (IV) followed by yttrium Y 90 basiliximab
      IV on day -14. Patients also receive carmustine IV on over 4 hours day -6, etoposide IV over
      1 hours once daily (QD) and cytarabine IV over 2 hours twice daily (BID) on days -5 to -2,
      and melphalan IV over 1 hours on day -1. Patients then receive hematopoietic progenitor cell
      apheresis (HPC-A) product via infusion on day 0. Beginning day 5, patients receive
      granulocyte colony-stimulating factor (G-CSF) (or biosimilar) subcutaneously (SC) or IV until
      absolute neutrophil count (ANC) > 500 for 3 consecutive days or according to the treating
      physician's best clinical judgement.

      After completion of study treatment, patients are followed up at 30 days, up to 2 years for
      response, and up to 5 years for survival.

Trial Arms

Name	Type	Description	Interventions
Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A)	Experimental	Patients receive 'cold' basiliximab IV followed by yttrium Y 90 basiliximab 0.6 mCi/kg IV on day -14. Patients also receive carmustine 300 mg/m2 IV on over 4 hours day -6, etoposide 200 mg/m2 IV over 1 hours QD and cytarabine 200 mg/m2 IV over 2 hours BID on days -5 to -2, and melphalan 140 mg/m2 IV over 1 hours on day -1. Patients then receive HPC-A product via infusion on day 0. Beginning day 5, patients receive G-CSF (or biosimilar) SC or IV until ANC > 500 for 3 consecutive days or according to the treating physician's best clinical judgement.	Basiliximab Carmustine Cytarabine Etoposide

Eligibility Criteria

        Inclusion Criteria:

          -  Documented informed consent of the participant and/or legally authorized
             representative

               -  Assent, when appropriate, will be obtained per institutional guidelines

          -  Age: >= 18 years

          -  Karnofsky performance status >= 70%

          -  Life expectancy >= 6 months

          -  Histologically confirmed Hodgkin lymphoma (HL)

          -  Relapsed/refractory disease

               -  PIF (primary induction failure): Did not enter complete remission with first line
                  of therapy. Note: a patient with PIF who responds to salvage therapy with a
                  partial response (PR) or complete response (CR) is also eligible (and would be
                  considered PIF-sensitive)

               -  Early 1st relapse: Initial CR of > 3 months and < 12 months after 1st line
                  chemotherapy

               -  1st relapsed HL in a patient who is not in CR after 2 different salvage therapy
                  regimens to attain CR

               -  In 2nd or subsequent RL whether in CR or not after salvage therapy

          -  High risk relapsed or refractory HL disease defined as having any one of the
             following:

               -  B symptoms at relapse

               -  Extranodal disease at relapse

               -  Primary refractory disease

               -  Relapse < 1 year after completion of frontline therapy

               -  Not in CR at the time of transplant

               -  Relapse after receiving PD1 blockade or brentuximab vedotin as initial therapy

          -  Patients will be enrolled after collection of at least 2.0 x 10^6 CD34 cells/kg of
             autologous hematopoietic progenitor cells (HPC-A) by apheresis

          -  Recovery from non-hematologic toxicities of salvage cytoreductive chemotherapy to =<
             grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5)

          -  Serum creatinine =< 1.5 mg/dL (performed prior to day 1 of protocol therapy)

          -  Creatinine clearance of >= 60 mL/min per 24 hour urine test =< 1.5 mg/dL (performed
             prior to day 1 of protocol therapy)

          -  Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
             (performed prior to day 1 of protocol therapy)

          -  Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) =< 1.5
             x ULN (except in cases where abnormal liver function tests (LFTs) are due to
             involvement with HL) (performed prior to day 1 of protocol therapy)

          -  Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 1.5 x
             ULN (except in cases where abnormal LFTs are due to involvement with HL) (performed
             prior to day 1 of protocol therapy)

          -  Left ventricular ejection fraction (LVEF) >= 50% (performed prior to day 1 of protocol
             therapy)

          -  Forced expiratory volume in 1 second (FEV1) > 65% of predicted measured, or DLCO
             (diffusion capacity) >= 50% of predicted measured (corrected for hemoglobin)
             (performed prior to day 1 of protocol therapy)

          -  Agreement by females and males of childbearing potential to use an effective method of
             birth control or abstain from heterosexual activity for the course of the study
             through at least six months after the last dose of protocol therapy

               -  Childbearing potential defined as not being surgically sterilized (men and women)
                  or have not been free from menses for > 1 year (women only)

        Exclusion Criteria:

          -  Planned BV consolidation after AHCT

          -  Prior high dose chemotherapy with autologous stem cell transplant, 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 principal
             investigator (PI)

          -  Patients may not be receiving any other investigational agents, or concurrent
             biological, chemotherapy, or radiation therapy

          -  Myelodysplasia or any active malignancy other than HL, or < 5 years remission from any
             other prior malignancy, except non-melanoma skin cancer, localized prostate cancer or
             localized cervical cancer

          -  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)

          -  Lymphocyte-predominant Hodgkin lymphoma

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to 90Y-basiliximab-DOTA

          -  Presence of antibodies against basiliximab (only required for patients who have
             received prior antibody therapy)

          -  Persistent marrow involvement (> 10%) with HL after salvage cytoreductive therapy and
             before stem cell mobilization

          -  Bone marrow (BM) harvest required to reach adequate cell dose for transplant

          -  Active hepatitis B or C viral infection or hepatitis B surface antigen positive

          -  Positive human immunodeficiency virus antibody, patients with undetectable human
             immunodeficiency virus (HIV) viral load with CD4 >= 300 and are on highly active
             antiretroviral therapy (HAART) medication are allowed

          -  Patients should not have any uncontrolled illness including ongoing or active
             infection

          -  Patients with psychosocial circumstances or illnesses that preclude protocol
             participation (to be determined by P.I.)

          -  Pregnant women are excluded from this study because 90Y-basiliximab/DOTA is an agent
             with the potential for teratogenic or abortifacient effects. Because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother 90Y-basiliximab/DOTA, breastfeeding should be discontinued if
             the mother is treated with 90Y-basiliximab/DOTA

          -  Any other condition that would, in the investigator's judgment, contraindicate the
             patient's participation in the clinical study due to safety concerns with clinical
             study procedures

          -  Any other condition that would, in the Investigator's judgment, contraindicate the
             patient's participation in the clinical study due to safety concerns with clinical
             study procedures

          -  Prospective participants who, in the opinion of the investigator, may not be able to
             comply with all study procedures (including compliance issues related to
             feasibility/logistics)

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

Primary Outcome Measures

Measure:	Progression free survival
Time Frame:	From the start of treatment up to 5 years post transplant
Safety Issue:
Description:	Disease relapse or progression, or death from any cause, whichever occurs first.

Secondary Outcome Measures

Measure:	Overall survival
Time Frame:	From the start of treatment up to 5 years post transplant
Safety Issue:
Description:	Death from any cause.

Measure:	Relapse or progression
Time Frame:	From the start of treatment up to 5 years post transplant
Safety Issue:
Description:	Relapse or progression of Hodgkin lymphoma.

Measure:	Non-relapse mortality
Time Frame:	From the start of treatment up to 5 years post transplant
Safety Issue:
Description:	Death from causes other than relapse or progression.

Measure:	Incidence of toxicities and adverse events
Time Frame:	Day -14 to day 100 post-transplant
Safety Issue:
Description:	Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity. Toxicities will be recorded using both the Bearman criteria and the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 scale.

Measure:	Time to hematopoietic recovery
Time Frame:	Up to day 100 post transplant
Safety Issue:
Description:	Time to neutrophil recovery will be the first of three consecutive days of ≥ 500 neutrophils/µL following the expected nadir. Time to platelet engraftment will be the first day of the first of three consecutive daily laboratory values when the platelet count is ≥20,000/µL, without a platelet transfusion in the previous seven days.

Measure:	Incidence of infection
Time Frame:	Day -14 to day 100 post-transplant
Safety Issue:
Description:	Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any.

Measure:	Rate of secondary myelodysplastic syndrome
Time Frame:	From the start of treatment up to 5 years post transplant
Safety Issue:
Description:	Secondary MDS or AML post therapy

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	City of Hope Medical Center

Last Updated

August 24, 2021

Clinical Trials /

Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Combined With BEAM Chemotherapy Conditioning for the Treatment of Primary Refractory or Relapsed Hodgkin Lymphoma