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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA022453 | U.S. NIH Grant/Contract | View source | |
| WSU-2007-034 | |||
| 2365-1186500223.02 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Giving high doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. Colony stimulating factors, such as aldesleukin and GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells that have been treated with antibodies after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells given together with low-dose aldesleukin and low-dose GM-CSF after donor stem cell transplant in treating patients with relapsed or refractory non-Hodgkin's lymphoma.
OBJECTIVES:
OUTLINE: All patients receive high-dose chemotherapy that is standard of care for their disease. Peripheral blood lymphocytes are obtained from the HLA-identical sibling donor and cultured to obtain activated T cells (ATC), some of which are subsequently armed with CD20 bispecific antibody (CD20Bi) and cryopreserved for later use. Patients then undergo allogeneic hematopoietic stem cell transplantation (SCT).
Patients receive ATC-CD20Bi IV on days 40, 70, 100, 130, and 160 after SCT. Patients receive low-dose aldesleukin subcutaneously (SC) once daily for 7 days beginning within 24 hours after each ATC-CD20Bi infusion and low-dose sargramostim (GM-CSF) SC every other day for 3 doses beginning within 24 hours after each infusion of ATC-CD20Bi. Patients also receive tacrolimus and mycophenolate mofetil as standard graft-vs-host disease prophylaxis. Treatment continues in the absence of unacceptable toxicity.
Some patients with well-defined or evaluable masses receive indium I 111 (^111I)-labeled ATC-CD20Bi IV and ^111I-labeled unarmed ATC and then undergo whole-body imaging for trafficking studies.
After completion of study treatment, patients are followed at 6 months, 12 months, and then annually thereafter.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells | Biological |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose | ||
| Time to relapse | ||
| Disease-free survival | ||
| Overall survival |
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DISEASE CHARACTERISTICS:
Histologically confirmed CD20-positive non-Hodgkin lymphoma
Must have an available HLA-identical sibling donor
No significant skin breakdown from tumor or other disease
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
DLCO ≥ 50% of normal
No symptomatic obstructive or restrictive pulmonary disease
Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min
Direct bilirubin ≤ 2.0 mg/dL (even if attributable to disease)
SGOT and SGPT ≤ 2.5 times normal (even if attributable to disease)
No history of severe hepatic dysfunction
No severe cardiac dysfunction
LVEF ≥ 50% by gated blood pool scan
No major heart disease
Patients with congenital or acquired heart disease or cardiac arrhythmias must undergo a cardiology consultation and evaluation
No active infections
HIV antibody negative
No uncompensated major thyroid or adrenal dysfunction
Not pregnant or nursing
Persistently elevated systolic blood pressure (BP) ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg must be controlled with antihypertensive agents for at least 7 days prior to initiation of cell therapy
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Lawrence G. Lum, MD, DSc | Barbara Ann Karmanos Cancer Institute | Principal Investigator |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D002051 | Burkitt Lymphoma |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D008228 | Lymphoma, Non-Hodgkin |
| D016400 | Lymphoma, Large-Cell, Immunoblastic |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D054218 | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma |
| D016410 | Lymphoma, T-Cell, Cutaneous |
| D008224 | Lymphoma, Follicular |
| D020522 | Lymphoma, Mantle-Cell |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D008258 | Waldenstrom Macroglobulinemia |
| D054391 | Lymphoma, Extranodal NK-T-Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D006402 | Hematologic Diseases |
| D016399 | Lymphoma, T-Cell |
| D015448 | Leukemia, B-Cell |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
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