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

  • STATUS
    Recruiting
  • End date
    Nov 16, 2026
  • participants needed
    33
  • sponsor
    City of Hope Medical Center
Updated on 7 July 2022

Summary

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.

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) or QD 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.

Details
Condition Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma
Treatment cytarabine, etoposide, autologous stem cell transplantation, Basiliximab, carmustine, Genetically Engineered Hematopoietic Stem Progenitor Cells, Yttrium Y 90 Basiliximab, Recombinant Granulocyte Colony-Stimulating Factor, Yttrium - 90 Basiliximab
Clinical Study IdentifierNCT04871607
SponsorCity of Hope Medical Center
Last Modified on7 July 2022

Eligibility

Yes No Not Sure

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
st 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)
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