Treatment for recurrent or refractory Hodgkin lymphoma using a combination of targeted therapy and chemotherapy
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
This study is testing a new combination of targeted therapy and chemotherapy to see if it can help people with recurring or stubborn Hodgkin lymphoma before they undergo a stem cell transplant.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 33 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | brentuximab, basiliximab, chemotherapy, radiation |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT04871607 on ClinicalTrials.gov |
What this trial studies
This phase II trial investigates the effectiveness of yttrium-90 labeled anti-CD25 monoclonal antibody combined with BEAM chemotherapy in patients with Hodgkin lymphoma that has either relapsed or is refractory to treatment. The study aims to evaluate the anti-lymphoma activity of this regimen as a conditioning treatment for autologous hematopoietic cell transplantation. Key objectives include assessing progression-free survival, overall survival, and the incidence of relapse or progression, as well as monitoring treatment-related toxicities and complications. Additionally, the trial will explore biological markers and their association with treatment outcomes.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with high-risk relapsed or refractory Hodgkin lymphoma.
Not a fit: Patients with low-risk Hodgkin lymphoma or those who are not eligible for autologous hematopoietic cell transplantation may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new effective option for patients with difficult-to-treat Hodgkin lymphoma.
How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination is being evaluated for the first time in this context.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria Informed Consent and Willingness to Participate 1. Documented informed consent of the participant and/or legally authorized representative.
\- Assent, when appropriate, will be obtained per institutional guidelines Age Criteria, Performance status
1. Age: ≥18 years
2. Karnofsky performance status ≥ 70%
3. Life expectancy ≥ 6 months Nature of Illness and Illness Related Criteria
4. Histologically confirmed HL
5. 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
6. Patients will be enrolled after collection of at least 2.0 x 106 CD34 cells/kg of autologous hematopoietic progenitor cells (HPC-A) by apheresis.
7. Recovery from non-hematologic toxicities of salvage cytoreductive chemotherapy to ≤ grade 2 (CTCAE v5).
Clinical Laboratory and Organ Function Criteria (To be performed prior to Day 1 of protocol therapy)
8. Serum creatinine ≤ 1.5 mg/dL
9. Creatinine clearance of ≥ 60 mL/min per 24 hour urine test
10. Total bilirubin ≤ 1.5 X ULN (unless has Gilbert's disease)
11. AST/SGOT ≤1.5 x ULN (except in cases where abnormal LFTs are due to involvement with HL)
12. ALT/SGPT ≤ 1.5 x ULN (except in cases where abnormal LFTs are due to involvement with HL)
13. Left ventricular ejection fraction (LVEF) ≥ 50%
14. FEV1 \> 65% of predicted measured, or DLCO (diffusion capacity) ≥ 50% of predicted measured (corrected for hemoglobin).
Contraception
15. 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 Prior and concomitant therapies
1. Planned BV consolidation after AHCT
2. Prior high dose chemotherapy with autologous stem cell transplant, or prior allogeneic transplantation.
3. 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.
4. Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
Other illnesses or conditions
5. 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
6. 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).
7. Lymphocyte-predominant Hodgkin Lymphoma
8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-basiliximab-DOTA.
9. Persistent marrow involvement (\>10%) with HL after salvage cytoreductive therapy and before stem cell mobilization.
10. BM harvest required to reach adequate cell dose for transplant.
11. Active Hepatitis B or C viral infection or Hepatitis B surface antigen positive
12. Positive Human Immunodeficiency Virus antibody, patients with undetectable HIV viral load with CD4 ≥ 300 and are on HAART medication are allowed
13. Patients should not have any uncontrolled illness including ongoing or active infection.
14. Patients with psychosocial circumstances or illnesses that preclude protocol participation (to be determined by P.I.)
15. 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.
16. 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.
Noncompliance
17. 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).
* Eligibility should be confirmed per institutional policies.
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
Study contacts
- Principal investigator: Alex F Herrera — City of Hope Medical Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.