Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Combined With BEAM Chemotherapy Conditioning for the Treatment of Primary Refractory or Relapsed Hodgkin Lymphoma
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| ClinicalTrials.gov Identifier: NCT04871607 |
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Recruitment Status :
Recruiting
First Posted : May 4, 2021
Last Update Posted : February 18, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent Hodgkin Lymphoma Refractory Hodgkin Lymphoma | Biological: Basiliximab Drug: Carmustine Drug: Cytarabine Drug: Etoposide Procedure: Autologous stem cell transplantation Radiation: Yttrium - 90 Basiliximab | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 33 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | November 2, 2021 |
| Estimated Primary Completion Date : | November 13, 2023 |
| Estimated Study Completion Date : | November 13, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (yttrium Y 90 basiliximab, chemotherapy, HPC-A)
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. |
Biological: Basiliximab
Anti-CD25 antibody given IV
Other Names:
Drug: Carmustine Cytotoxic chemotherapy; alkylating agent given IV
Other Names:
Drug: Cytarabine Cytotoxic chemotherapy; antimetabolite given IV
Other Names:
Drug: Etoposide Cytotoxic chemotherapy; topoisomerase II inhibitor given IV
Other Names:
Procedure: Autologous stem cell transplantation Patients will receive their own stem cells, collected prior to conditioning given via IV infusion Radiation: Yttrium - 90 Basiliximab Radio-conjugate of anti-CD25 antibody given IV
Other Name: 90Y Basiliximab |
- Progression free survival [ Time Frame: From the start of treatment up to 5 years post transplant ]Disease relapse or progression, or death from any cause, whichever occurs first.
- Overall survival [ Time Frame: From the start of treatment up to 5 years post transplant ]Death from any cause.
- Relapse or progression [ Time Frame: From the start of treatment up to 5 years post transplant ]Relapse or progression of Hodgkin lymphoma.
- Non-relapse mortality [ Time Frame: From the start of treatment up to 5 years post transplant ]Death from causes other than relapse or progression.
- Incidence of toxicities and adverse events [ Time Frame: Day -14 to day 100 post-transplant ]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.
- Time to hematopoietic recovery [ Time Frame: Up to day 100 post transplant ]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.
- Incidence of infection [ Time Frame: Day -14 to day 100 post-transplant ]Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any.
- Rate of secondary myelodysplastic syndrome [ Time Frame: From the start of treatment up to 5 years post transplant ]Secondary MDS or AML post therapy
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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)
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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
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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)
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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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04871607
| United States, California | |
| City of Hope Medical Center | Recruiting |
| Duarte, California, United States, 91010 | |
| Contact: Alex F. Herrera 626-256-4673 ext 62405 aherrera@coh.org | |
| Principal Investigator: Alex F. Herrera | |
| Principal Investigator: | Alex F Herrera | City of Hope Comprehensive Cancer Center |
| Responsible Party: | City of Hope Medical Center |
| ClinicalTrials.gov Identifier: | NCT04871607 |
| Other Study ID Numbers: |
20420 NCI-2021-03073 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 20420 ( Other Identifier: City of Hope Medical Center ) P30CA033572 ( U.S. NIH Grant/Contract ) |
| First Posted: | May 4, 2021 Key Record Dates |
| Last Update Posted: | February 18, 2022 |
| Last Verified: | February 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Lymphoma Hodgkin Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Etoposide Podophyllotoxin Etoposide phosphate Carmustine Basiliximab Antineoplastic Agents, Phytogenic |
Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Alkylating Alkylating Agents Keratolytic Agents |