Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Cancer, Kidney Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 4/2/2016 |
| Start Date: | January 1999 |
A Phase II Study of HLA-Matched Peripheral Blood Mobilized Hematopoietic Progenitor Cell Transplantation for Metastatic Renal Cell Carcinoma Followed by Allogeneic T-Cell Infusion as Adoptive Immunotherapy
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine,
before a donor peripheral blood stem cell transplant helps stop the growth of tumor cells.
It may also stop the patient's immune system from rejecting the donor's stem cells. The
donated stem cells may replace the patient's immune cells and help destroy any remaining
tumor cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor
lymphocyte infusion) 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 cyclosporine with or without mycophenolate mofetil or methotrexate after the
transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well peripheral stem cell transplant works in
treating patients with metastatic kidney cancer.
before a donor peripheral blood stem cell transplant helps stop the growth of tumor cells.
It may also stop the patient's immune system from rejecting the donor's stem cells. The
donated stem cells may replace the patient's immune cells and help destroy any remaining
tumor cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor
lymphocyte infusion) 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 cyclosporine with or without mycophenolate mofetil or methotrexate after the
transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well peripheral stem cell transplant works in
treating patients with metastatic kidney cancer.
OBJECTIVES:
- Determine the antitumor effect of allogeneic peripheral blood stem cell transplantation
(PBSCT) in patients with metastatic renal cell carcinoma.
- Evaluate the safety and toxicity of a nonmyeloablative, low-intensity, preparative
regimen followed by an HLA-matched allogeneic PBSCT in these patients.
- Determine engraftment by measuring donor-recipient chimerism in lymphoid and myeloid
lineages in patients treated with this regimen.
- Determine the relationship between donor-host chimerism and the incidence of acute and
chronic graft-versus-host disease in patients treated with this regimen.
- Determine the effect of lymphocyte infusions on donor-host chimerism in this patient
population.
- Determine the response rate, disease-free survival, overall survival, and mortality
from the procedure or tumor progression in patients treated with this regimen.
OUTLINE:
- Nonmyeloablative preparative regimen: Patients receive 1 of 3 preparative regimens
prior to peripheral blood progenitor cell (PBPC) transplantation. (Regimens 2 and 3
closed to accrual as of 10/1/03.)
- Regimen 1: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and
fludarabine IV over 30 minutes on days -5 to -1.
- Regimen 2 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV
over 1 hour on days -7 and -6, fludarabine IV over 30 minutes on days -5 to -1,
and antithymocyte globulin on days -5 to -2.
- Regimen 3 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV
over 1 hour on days -8 to -6, fludarabine IV over 30 minutes on days -5 to -1, and
antithymocyte globulin on days -5 to -2.
- PBPC transplantation: Patients undergo mobilized CD34+ PBPC transplantation on day 0.
PBPC transplantation may be repeated on days 1 and 2, if deemed necessary.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive 1 of 3 GVHD prophylaxis
regimens.
- Regimen 1 (closed to accrual as of 10/17/00): Patients receive cyclosporine IV
over 12 hours or orally beginning on day -4 and continuing for up to approximately
3 months.
- Regimen 2 (open to accrual from 10/17/00 through 2/11/02): Patients receive
cyclosporine as in regimen 1. Patients also receive mycophenolate mofetil.
- Regimen 3 (open to accrual as of 2/11/02): Patients receive cyclosporine as in
regimen 1. Patients also receive methotrexate.
- Donor lymphocyte infusions: Patients with progressive disease on days 15-30, day 60, or
day 100, without GVHD, receive infusion(s) of donor lymphocytes. Further donor
lymphocyte infusions after day 100 may be given at the discretion of the attending
physician.
Patients are followed every 2 months for 6 months, every 3 months for 2 years, and then
every 6 months for 2½ years.
PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
- Determine the antitumor effect of allogeneic peripheral blood stem cell transplantation
(PBSCT) in patients with metastatic renal cell carcinoma.
- Evaluate the safety and toxicity of a nonmyeloablative, low-intensity, preparative
regimen followed by an HLA-matched allogeneic PBSCT in these patients.
- Determine engraftment by measuring donor-recipient chimerism in lymphoid and myeloid
lineages in patients treated with this regimen.
- Determine the relationship between donor-host chimerism and the incidence of acute and
chronic graft-versus-host disease in patients treated with this regimen.
- Determine the effect of lymphocyte infusions on donor-host chimerism in this patient
population.
- Determine the response rate, disease-free survival, overall survival, and mortality
from the procedure or tumor progression in patients treated with this regimen.
OUTLINE:
- Nonmyeloablative preparative regimen: Patients receive 1 of 3 preparative regimens
prior to peripheral blood progenitor cell (PBPC) transplantation. (Regimens 2 and 3
closed to accrual as of 10/1/03.)
- Regimen 1: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and
fludarabine IV over 30 minutes on days -5 to -1.
- Regimen 2 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV
over 1 hour on days -7 and -6, fludarabine IV over 30 minutes on days -5 to -1,
and antithymocyte globulin on days -5 to -2.
- Regimen 3 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV
over 1 hour on days -8 to -6, fludarabine IV over 30 minutes on days -5 to -1, and
antithymocyte globulin on days -5 to -2.
- PBPC transplantation: Patients undergo mobilized CD34+ PBPC transplantation on day 0.
PBPC transplantation may be repeated on days 1 and 2, if deemed necessary.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive 1 of 3 GVHD prophylaxis
regimens.
- Regimen 1 (closed to accrual as of 10/17/00): Patients receive cyclosporine IV
over 12 hours or orally beginning on day -4 and continuing for up to approximately
3 months.
- Regimen 2 (open to accrual from 10/17/00 through 2/11/02): Patients receive
cyclosporine as in regimen 1. Patients also receive mycophenolate mofetil.
- Regimen 3 (open to accrual as of 2/11/02): Patients receive cyclosporine as in
regimen 1. Patients also receive methotrexate.
- Donor lymphocyte infusions: Patients with progressive disease on days 15-30, day 60, or
day 100, without GVHD, receive infusion(s) of donor lymphocytes. Further donor
lymphocyte infusions after day 100 may be given at the discretion of the attending
physician.
Patients are followed every 2 months for 6 months, every 3 months for 2 years, and then
every 6 months for 2½ years.
PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
- Histologically proven metastatic renal cell carcinoma not amenable to complete
surgical resection and progressive despite immunotherapy
- Bidimensionally evaluable clinically or radiographically
- HLA 6/6 or 5/6 matched family donor available
- No CNS metastases
PATIENT CHARACTERISTICS:
Age:
- 18 to 80
Performance status:
- ECOG 0 or 1
Life expectancy:
- At least 3 months
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin no greater than 4 mg/dL
- Transaminases no greater than 3 times upper limit of normal
Renal:
- Creatinine no greater than 2.5 mg/dL
- No malignancy-associated hypercalcemia (< 2.5 mmol/L)
Cardiovascular:
- Left ventricular ejection fraction greater than 40%
Pulmonary:
- DLCO greater than 65% of predicted
Other:
- Not pregnant
- HIV negative
- No major organ dysfunction that would preclude transplantation
- No other malignancies except basal cell or squamous cell skin cancer
- No psychiatric disorder or mental deficiency that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
Chemotherapy
- Not specified
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- At least 1 month since prior treatment for renal cell carcinoma
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