Know Cancer

or
forgot password

Submyeloablative Allogeneic Blood Stem Cell Transplantation With HLA Identical Donor Lymphocyte Infusions From Matched Related and Matched Unrelated Donors for Treatment of Metastatic Renal Cell Carcinoma


Phase 2
18 Years
65 Years
Not Enrolling
Both
Kidney Cancer

Thank you

Trial Information

Submyeloablative Allogeneic Blood Stem Cell Transplantation With HLA Identical Donor Lymphocyte Infusions From Matched Related and Matched Unrelated Donors for Treatment of Metastatic Renal Cell Carcinoma


OBJECTIVES:

- Determine the feasibility of submyeloablative HLA-identical allogeneic peripheral blood
stem cell transplantation in patients with metastatic or recurrent renal cell
carcinoma.

- Determine the toxicity of this regimen, in terms of incidence and severity of graft
rejection, acute graft-vs-host disease (GVHD), chronic GVHD, adverse effects from the
preparative regimen and thalidomide, and infection and bleeding, in these patients.

- Determine the efficacy of this regimen, in terms of objective partial and complete
response rates, in these patients.

- Determine the engraftment rates and extent of chimerism in patients treated with this
regimen.

- Determine the overall survival and time to treatment failure rate in patients treated
with this regimen.

- Determine the impact of thalidomide on the treatment of chronic GVHD in patients
treated with this regimen.

OUTLINE: Patients are stratified according to risk (low vs high).

Patients receive fludarabine IV over 30 minutes once daily on days -4 to -2 followed by
total body irradiation on day -1. Patients receive tacrolimus IV over 24 hours or orally
daily on days -3 to 35 and oral mycophenolate mofetil twice daily on days -3 to 28 as
graft-vs-host disease (GVHD) prophylaxis. Patients undergo allogeneic peripheral blood stem
cell transplantation over 1-2 hours on day 0.

Patients maintaining a mixed chimerism with no evidence of grade III or IV GVHD receive
donor lymphocyte infusions (DLI) on days 60, 90, and 120. Patients may receive additional
DLI as needed. Patients with limited chronic GVHD receive oral thalidomide daily beginning
after day 80 and continuing for 1 year or until disease progression or resolution of chronic
GVHD.

Patients are followed at 1, 3, 6, and 12 months and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 20-40 patients (10-20 per stratum) will be accrued for this
study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed renal cell carcinoma (RCC)

- Histology demonstrates major clear cell component

- Metastatic (stage IV) or recurrent disease

- Prior debulking nephrectomy required

- Disease not amenable to complete surgical resection

- Must have HLA-identical donor

- Matched related sibling donors must have 6/6 serologic HLA A, B, and DR match
with molecular confirmation at DRB1

- A 5/6 serologic mismatch with one antigen mismatch at locus A or B (not DR)
with molecular confirmation at locus A, B, and DRB1 allowed

- Matched unrelated donors must have a minimum of 8 out of 10 molecular matches at
loci A, B, C, DRB1, and DQB1

- No brain metastases

- Negative MRI required

PATIENT CHARACTERISTICS:

Age:

- 18 to 65

Performance status:

- Karnofsky 80-100% OR

- ECOG 0-1

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin less than 2 times upper limit of normal (ULN)

- ALT/AST less than 2 times ULN

- Alkaline phosphatase less than 2 times ULN

- Hepatitis A, B, and C negative

Renal:

- Creatinine clearance greater than 50 mL/min

- Calcium less than 10.5 mg/dL (bisphosphonates allowed)

Cardiovascular:

- LVEF no less than 10% below lower limit of normal

Pulmonary:

- FEV_1 and DLCO greater than 50%

Other:

- HIV negative

- No active bacterial, fungal, or viral (including cytomegalovirus) infections

- No intolerance or allergy to tacrolimus, mycophenolate mofetil, or fludarabine

- No intolerance to 200 cGy of total body irradiation

- No other serious comorbid disease, neurologic condition, or psychosocial condition
that would preclude study follow-up

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception for at least 1 month before,
during, and for at least 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Prior interleukin-2 allowed

- Prior interferon alfa allowed

Chemotherapy:

- Prior chemotherapy allowed

- No other concurrent chemotherapy for RCC

Endocrine therapy:

- No concurrent corticosteroids for other comorbid disease

Radiotherapy:

- No prior extensive radiotherapy to marrow microenvironment greater than 20% of total
marrow mass

- No prior radiotherapy that has reached tissue tolerance for heart, lung, liver,
kidney, or spinal cord

Surgery:

- See Disease Characteristics

Other:

- No other concurrent therapy for RCC

- No concurrent enrollment on another investigational protocol for treatment of RCC

- No other concurrent immunosuppressive medications

- No other concurrent investigational drugs

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Gary R. Hudes, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fox Chase Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000068970

NCT ID:

NCT00025519

Start Date:

June 2001

Completion Date:

Related Keywords:

  • Kidney Cancer
  • stage IV renal cell cancer
  • recurrent renal cell cancer
  • clear cell renal cell carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms

Name

Location

Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Fox Chase - Temple Cancer CenterPhiladelphia, Pennsylvania  19111-2442