Radiolabeled Monoclonal Antibody Therapy and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Primary Refractory or Relapsed Hodgkin Lymphoma

NCT01476839 | Completed Phase 1 DMC

• 4 other identifiers: 08179NCI-2011-03334P01CA030206R21CA185875-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I clinical trial studies the side effects and best dose of radiolabeled monoclonal antibody therapy when given together with combination chemotherapy before stem cell transplant and to see how well it works in treating patients with primary refractory (did not respond to treatment) or relapsed (returned after treatment) Hodgkin lymphoma. Radiolabeled monoclonal antibodies can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, 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 stopping them from spreading. Giving radiolabeled monoclonal antibody therapy together with combination chemotherapy may kill more cancer cells

Conditions

Recurrent Adult Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• RP2D of Yttrium-90 labeled basiliximab

  RP2D will generally be the highest maximum tolerated dose (MTD), but it may be less than the MTD based on a review of available data/cumulative toxicities. Additional pulmonary toxicity monitoring will be performed among enrolled/treated patients with prior brentuximab vedotin exposure for both portions of the study.

  Up to 18 months

• DLT

  Toxicities will be recorded using two distinct grading systems: the modified Bearman Scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0 scale. Observed toxicities will be summarized by type, severity, date of onset, duration (for neutropenia only), and attribution.

  For 30 days post-transplant

Secondary Outcomes (8)

• Best ORR

  Up to 5 years

• Biodistribution of basiliximab

  Pre-basiliximab infusion; pre radiolabeled basiliximab infusion; 2 and 4-6 hours post radiolabeled basiliximab infusion; and then 1, 2, 3-4, 5, and 6 days post radiolabeled basiliximab infusion

• Cumulative incidence of non-relapsed mortality (NRM)

  From stem cell infusion to death from any cause other than disease relapse or progression, assessed up to 5 years

• Cumulative incidence of relapse/progression incidence

  Up to 5 years

• Incidence of toxicity

  Up to 100 days post-infusion

Study Arms (1)

Treatment (radiolabeled monoclonal antibody, chemotherapy)

EXPERIMENTAL

DOSIMETRY STUDY: Patients receive basiliximab IV and indium In 111 basiliximab IV on day -21. Patients undergo indium In 111 imaging scans daily. Patients with appropriate biodistribution continue on to treatment. TREATMENT: Patients receive basiliximab IV and yttrium Y 90 basiliximab IV on day -14. Patients also receive BEAM chemotherapy comprising carmustine IV over 2 hours on days -7 and -6, etoposide IV BID over 4 hours and cytarabine IV over 2 hours BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic progenitor cell infusion on day 0.

Biological: basiliximab; Drug: carmustine; Drug: etoposide; Drug: cytarabine; Drug: melphalan; Other: pharmacological study; Other: laboratory biomarker analysis; Procedure: autologous hematopoietic stem cell transplantation; Biological: yttrium Y 90-labeled basiliximab

Interventions

basiliximab BIOLOGICAL

Given IV

Also known as: SDZ-CHI-621, Simulect

Treatment (radiolabeled monoclonal antibody, chemotherapy)

carmustine DRUG

Given IV

Also known as: BCNU, BiCNU, bis-chloronitrosourea

Treatment (radiolabeled monoclonal antibody, chemotherapy)

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

Treatment (radiolabeled monoclonal antibody, chemotherapy)

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Treatment (radiolabeled monoclonal antibody, chemotherapy)

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

Treatment (radiolabeled monoclonal antibody, chemotherapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (radiolabeled monoclonal antibody, chemotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (radiolabeled monoclonal antibody, chemotherapy)

autologous hematopoietic stem cell transplantation PROCEDURE

Undergo autologous hematopoietic progenitor cell infusion

Treatment (radiolabeled monoclonal antibody, chemotherapy)

yttrium Y 90-labeled basiliximab BIOLOGICAL

Given IV

Also known as: 90Y basiliximab

Treatment (radiolabeled monoclonal antibody, chemotherapy)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathology confirmation of HL with City of Hope (COH) pathology review
• Hodgkin lymphoma that is:
• 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 PR or 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 cycles of salvage therapy
• In 2nd or subsequent relapse (RL) whether in CR or not after salvage therapy
• Relapse/persistent disease evidenced by a computed tomography and fluorodeoxyglucose (FDG)-positron emission tomography (PET), or bone marrow biopsy
• 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 diffusion capacity of the lung for carbon monoxide (DLCO) \>= 50% of predicted measured
• Bilirubin =\< 1.5 x normal
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =\< 2 x normal except in cases where abnormal liver function tests (LFTS) are due to involvement with HL
• Serum creatinine of =\< 1.5 mg/dL, and a measured creatinine clearance of \>= 60 mL/min
• Karnofsky status \>= 70%
• Life expectancy \>= 6 months
• Females must not be pregnant or breast feeding, and must use accepted birth control methods; males must use accepted birth control methods

You may not qualify if:

• Lymphocyte-predominant Hodgkin lymphoma
• 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 PI; patients who have had prior external beam radiation \> 2000 cGy (at 180 to 200 cGy per day) to any portion of the lung will be ineligible; patients with ANY prior radiation to the heart are ineligible; patients with \> 500 cGy to any portion of the kidney will be excluded from the study
• Presence of antibody against basiliximab (only required for patients who have received prior antibody)
• Myelodysplasia or any active malignancy other than HL, or \< 5 years remission from any other prior malignancy, except adequately treated basal cell or squamous cell carcinoma
• Active hepatitis B or C viral infection or hepatitis B surface antigen positive
• Positive human immunodeficiency virus antibody
• Patients with psychosocial circumstances or illnesses that preclude protocol participation (to be determined by PI)
• Co-morbid illnesses that preclude protocol participation (to be determined by PI)
• 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)
• Persistent marrow involvement (\> 10%) with HL after salvage cytoreductive therapy and before stem cell mobilization
• Systemic chemotherapy or radiation within 4 weeks prior to the Y-90 dose of radioimmunotherapy (RIT), with the exception of single agent Cytoxan priming chemotherapy administered for mobilization
• Bone marrow (BM) harvest required to reach adequate cell dose for transplant

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

• Herrera AF, Palmer J, Adhikarla V, Yamauchi D, Poku EK, Bading J, Yazaki P, Dandapani S, Mei M, Chen R, Cao T, Karras N, McTague P, Nademanee A, Popplewell L, Sahebi F, Shively JE, Simpson J, Smith DL, Song J, Spielberger R, Tsai NC, Thomas SH, Forman SJ, Colcher D, Wu AM, Wong J, Smith E. Anti-CD25 radioimmunotherapy with BEAM autologous hematopoietic cell transplantation conditioning in Hodgkin lymphoma. Blood Adv. 2021 Dec 14;5(23):5300-5311. doi: 10.1182/bloodadvances.2021004981.

  PMID: 34638132 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Basiliximab; Carmustine; Etoposide; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Eileen Smith

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2011
• First Posted: November 22, 2011
• Study Start: November 9, 2012
• Primary Completion: July 24, 2021
• Study Completion: May 31, 2024
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

US (1)