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Donor T Cells, Low-Dose Aldesleukin, and Low-Dose GM-CSF After Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Primary Purpose

Lymphoma

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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 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 small lymphocytic lymphoma, Waldenstrom macroglobulinemia, adult nasal type extranodal NK/T-cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, cutaneous B-cell non-Hodgkin lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Histologically confirmed CD20-positive non-Hodgkin lymphoma
- Relapsed, resistant, or chemorefractory disease
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
- Patients who have not been seen and evaluated by a dentist for teeth cleaning and examination for potential sources of infection are ineligible
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
- Patients with essential hypertension that is controlled with medication are eligible

PRIOR CONCURRENT THERAPY:

Prior total dose of doxorubicin or daunorubicin must have been less than 450 mg/m^2 unless an endomyocardial biopsy shows less than grade 2 drug effect
No concurrent nitroglycerin preparations for angina pectoris
No antiarrhythmic drugs for major ventricular dysrhythmias

Sites / Locations

Outcomes

Primary Outcome Measures

Maximum tolerated dose

Time to relapse

Disease-free survival

Overall survival

Secondary Outcome Measures

Full Information

NCT ID

NCT00521261

First Posted

August 24, 2007

Last Updated

March 4, 2014

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00521261

Brief Title

Donor T Cells, Low-Dose Aldesleukin, and Low-Dose GM-CSF After Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Official Title

Immune Consolidation With Allogeneic Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) After Allogeneic Peripheral Blood Stem Cell Transplant for High Risk CD20+ Non-Hodgkin's Lymphoma (Phase I)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Withdrawn

Study Start Date

October 2007 (undefined)

Primary Completion Date

July 2008 (Actual)

Study Completion Date

July 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

OBJECTIVES: Determine the maximum tolerated dose of donor-derived allogeneic anti-CD3 X anti-CD20 bispecific antibody (CD20Bi)-armed activated T cells (ATC) when given with low-dose aldesleukin and low-dose sargramostim (GM-CSF) after allogeneic stem cell transplantation in patients with relapsed or refractory CD20-positive non-Hodgkin lymphoma. Perform trafficking studies using indium I 111-labeled unarmed ATC and ATC armed with CD20Bi in patients with evaluable lymphoma sites to determine whether armed ATC specifically traffic to tumor sites and correlate these data with CT and PET scans. Evaluate immune responses and immune reconstitution of T and B cells. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

Keywords

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 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 small lymphocytic lymphoma, Waldenstrom macroglobulinemia, adult nasal type extranodal NK/T-cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, cutaneous B-cell non-Hodgkin lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells

Primary Outcome Measure Information:

Title

Maximum tolerated dose

Title

Time to relapse

Title

Disease-free survival

Title

Overall survival

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically confirmed CD20-positive non-Hodgkin lymphoma Relapsed, resistant, or chemorefractory disease 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 Patients who have not been seen and evaluated by a dentist for teeth cleaning and examination for potential sources of infection are ineligible 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 Patients with essential hypertension that is controlled with medication are eligible PRIOR CONCURRENT THERAPY: Prior total dose of doxorubicin or daunorubicin must have been less than 450 mg/m^2 unless an endomyocardial biopsy shows less than grade 2 drug effect No concurrent nitroglycerin preparations for angina pectoris No antiarrhythmic drugs for major ventricular dysrhythmias

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lawrence G. Lum, MD, DSc

Organizational Affiliation

Barbara Ann Karmanos Cancer Institute

Official's Role

Principal Investigator

12. IPD Sharing Statement

Learn more about this trial

Donor T Cells, Low-Dose Aldesleukin, and Low-Dose GM-CSF After Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

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