Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Refractory Hairy Cell Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Waldenström Macroglobulinemia
Conditions
Brief summary
This phase I trial studies the side effects and best dose of monoclonal antibody therapy before stem cell transplant in treating patients with relapsed or refractory lymphoid malignancies. Radiolabeled monoclonal antibodies, such as yttrium-90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving radiolabeled monoclonal antibody before a stem cell transplant may be an effective treatment for relapsed or refractory lymphoid malignancies.
Detailed description
PRIMARY OBJECTIVES: I. To estimate the maximally tolerated dose (MTD) of 90Y-BC8-DOTA (anti-cluster of differentiation \[CD\]45) (yttrium-90 anti-CD45 monoclonal antibody BC8) that can be delivered prior to autologous stem cell transplantation for patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), T-cell NHL (T-NHL), and Hodgkin lymphoma (HL). SECONDARY OBJECTIVES: I. To optimize the protein dose (antibody \[Ab\]) to deliver a favorable biodistribution in the majority of patients. II. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden on CD20 and CD45 targeting. III. To describe response rates and remission durations in relapsed B-NHL, T-NHL, and HL following administration of myeloablative doses of 90Y-BC8-DOTA prior to autologous stem cell transplant (ASCT). IV. To assess the correlation of lymphoma biomarkers with outcomes. OUTLINE: This is a dose-escalation study of yttrium-90 anti-CD45 monoclonal antibody BC8. Patients receive indium-111 anti-CD45 monoclonal antibody BC8 intravenously (IV) on day -28 and (if necessary) day -21 to evaluate the antibody's biodistribution. Patients then receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients then undergo autologous peripheral blood stem cell transplantation on day 0. After completion of study treatment, patients are followed up at 3, 6, and 12 months and then annually thereafter.
Interventions
Given IV
Given IV
Undergo autologous peripheral blood stem cell transplant
Sponsors
Study design
Eligibility
Inclusion criteria
* Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only patients with classical HL must have documented histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells; patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease; patients with mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1) * Creatinine \< 2.0 * Bilirubin \< 1.5 mg/dL * All patients eligible for therapeutic study must have a minimum of \>= 2 x 10\^6 CD34/kg autologous hematopoietic stem cells harvested and cryopreserved * Patients must have an expected survival of \> 60 days and must be free of major infection * Patients are preferred to have either a tumor mass amenable to core needle biopsy during the dosimetry phase, or a measurable tumor mass with at least one site of involvement measuring 2.5 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission computed tomography (SPECT)/CT tumor dosimetry
Exclusion criteria
* Circulating human anti-mouse antibody (HAMA), to be determined before each infusion * Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab * Inability to understand or give an informed consent * Lymphoma involving the central nervous system * Other serious medical conditions considered to represent contraindications to ASCT (e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide \[DLCO\] \< 50% predicted, acquired immune deficiency syndrome \[AIDS\], etc.) * Known human immunodeficiency virus (HIV) seropositivity * Pregnancy or breast feeding * Prior allogeneic bone marrow or stem cell transplant * Prior autologous bone marrow or stem cell transplant within 1 year of enrollment * Prior radiation therapy (RT) \> 20 Gray (Gy) to a critical organ within 1 year of enrollment * Southwest Oncology Group (SWOG) performance status \>= 2.0 * Patients with relapsed diffuse large B-cell lymphoma (DLBCL) or HL that have achieved a positron emission tomography (PET)-negative CR following first salvage chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45 | Up to 30 days after receiving study drug | A DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 6 years | — |
| Progression-free Survival | Up to 6 years | — |
| Overall Response Rate | Up to 6 years | — |
| Tumor to Normal Organ Ratios | Up to 6 years | Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8) Patients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
indium In 111 anti-CD45 monoclonal antibody BC8: Given IV
yttrium Y 90 anti-CD45 monoclonal antibody BC8: Given IV
peripheral blood stem cell transplantation: Undergo autologous peripheral blood stem cell transplant | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8) |
|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45
A DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant.
Time frame: Up to 30 days after receiving study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8) | Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45 | 0 Participants |
Overall Response Rate
Time frame: Up to 6 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8) | Overall Response Rate | 0 Participants |
Overall Survival
Time frame: Up to 6 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8) | Overall Survival | 750.5 days |
Progression-free Survival
Time frame: Up to 6 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Yttrium-90 Anti-CD45 Monoclonal Antibody BC8) | Progression-free Survival | 0 Participants |
Tumor to Normal Organ Ratios
Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.
Time frame: Up to 6 years
Population: This outcome measure was not done. Only two patients were enrolled before the study was closed early. Tumor to normal organ ratios was not determined due to small sample size.