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

NCT ID: NCT00027573

Last Updated: 2016-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-10-31
• Study Completion Date: 2006-06-30

Brief Summary

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.

Detailed 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.

Conditions

Kidney Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemotherapy + stem cell transplantation

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.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

therapeutic allogeneic lymphocytes

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

tacrolimus

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

therapeutic allogeneic lymphocytes

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

tacrolimus

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian I. Rini, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

CCOP - Mayo Clinic Scottsdale Oncology Program

Scottsdale, Arizona, United States

Indiana University Cancer Center

Indianapolis, Indiana, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

CCOP - Oklahoma

Tulsa, Oklahoma, United States

Countries

United States

References

Rini BI, Halabi S, Barrier R, Margolin KA, Avigan D, Logan T, Stadler WM, McCarthy PL, Linker CA, Small EJ; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; Southwestern Oncology Group. Adoptive immunotherapy by allogeneic stem cell transplantation for metastatic renal cell carcinoma: a CALGB intergroup phase II study. Biol Blood Marrow Transplant. 2006 Jul;12(7):778-85. doi: 10.1016/j.bbmt.2006.03.011.

Reference Type: RESULT

PMID: 16785067 (View on PubMed)

Other Identifiers

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-90003

Identifier Type: -

Identifier Source: secondary_id

CDR0000069044

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-90003

Identifier Type: -

Identifier Source: org_study_id