Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Metastatic or Unresectable Kidney Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Kidney Cancer

Treatments: Drug: tacrolimus; Drug: fludarabine phosphate; Biological: therapeutic allogeneic lymphocytes; Biological: filgrastim; Drug: cyclophosphamide; Procedure: peripheral blood stem cell transplantation; Drug: methotrexate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00027573

CDR0000069044 (Registry Identifier)

U10CA031946 (U.S. NIH Grant/Contract)

CALGB-90003

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have metastatic or unresectable kidney cancer.

Full description

OBJECTIVES:

• Determine the overall response rate and overall and disease-free survival of patients with unresectable or metastatic renal cell cancer treated with fludarabine and cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation.
• Determine the toxicity and treatment-related mortality of this regimen in these patients.
• Determine the percentage of donor chimerism in patients treated with this regimen.

Enrollment: 36 patients

Sex: All

Ages: Under 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma (RCC)

  • Clear cell or papillary RCC
  • Granular tumors with sarcomatoid features
  • No purely sarcomatoid RCC, chromophobic RCC, or oncocytoma
  • No transitional cell carcinoma of the renal pelvis and collecting systems

• Metastatic or unresectable disease

• At least 1 measurable lesion

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

  • The following are not considered measurable:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
    • Primary bladder masses

• Progressive disease after interferon alfa and/or interleukin-2 for metastatic RCC OR intolerance to these therapies

• No prior or concurrent CNS metastases

  • Negative MRI of the brain within the past 28 days

• Must have HLA-identical (6/6) sibling donor

PATIENT CHARACTERISTICS:

Age:

• 60 and under

Performance status:

• ECOG 0-1

Life expectancy:

• More than 6 months

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal:

• Creatinine clearance at least 40 mL/min

Cardiovascular:

• LVEF at least 45% by MUGA or echocardiogram

Pulmonary:

• DLCO greater than 40% of predicted (corrected for hemoglobin level)
• No symptomatic pulmonary disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No known hypersensitivity to E. coli-derived products
• No uncontrolled diabetes mellitus
• No active serious infection
• No other concurrent malignancy except non-melanoma skin cancer or other malignancy that has less than a 30% risk of relapse after completion of therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No concurrent sargramostim (GM-CSF)
• Concurrent epoetin alfa allowed

Chemotherapy:

• No other concurrent chemotherapy

Endocrine therapy:

• At least 28 days since prior hormonal therapy (e.g., megestrol, corticosteroids, or anti-estrogen therapy)
• Concurrent steroids allowed for adrenal failure, graft-versus-host disease, or other nondisease-related conditions (e.g., insulin for diabetes)

Radiotherapy:

• At least 14 days since prior radiotherapy

Surgery:

• At least 14 days since prior surgery

Other:

• At least 28 days since prior systemic therapy for RCC
• Recovered from prior therapy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

Chemotherapy + stem cell transplantation

Experimental group

Description:

Patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1-2 hours on days -4 and -3. Allogeneic peripheral blood stem cells are infused on day 0. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 5 and continuing until blood counts recover. Patients receive graft-versus-host disease (GVHD) prophylaxis comprising oral tacrolimus twice daily on days -1 to 90 and methotrexate IV on days 1, 3, and 6. After day 120, patients with persistent disease and no signs of active GVHD may receive donor lymphocyte infusion (DLI). DLI may be repeated every 8 weeks for a total of 2 infusions. Patients are followed every 2 months for 1 year and then every 6 months for 4 years OR every 2 months for 6 months and then every 6 months for 4.5 years if patient receives DLI.

Treatment:

Drug: tacrolimus

Drug: fludarabine phosphate

Drug: cyclophosphamide

Drug: methotrexate

Biological: filgrastim

Procedure: peripheral blood stem cell transplantation

Biological: therapeutic allogeneic lymphocytes