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

Primary Purpose

Kidney Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
filgrastim
therapeutic allogeneic lymphocytes
cyclophosphamide
fludarabine phosphate
methotrexate
tacrolimus
peripheral blood stem cell transplantation
Sponsored by
Alliance for Clinical Trials in Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Cancer focused on measuring stage IV renal cell cancer, recurrent renal cell cancer, clear cell renal cell carcinoma, papillary renal cell carcinoma

Eligibility Criteria

undefined - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CCOP - Mayo Clinic Scottsdale Oncology Program
  • Indiana University Cancer Center
  • Beth Israel Deaconess Medical Center
  • Mayo Clinic Cancer Center
  • CCOP - Northern New Jersey
  • CCOP - Oklahoma

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemotherapy + stem cell transplantation

Arm 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.

Outcomes

Primary Outcome Measures

Overall response rate
Overall survival
Disease-free survival
Treatment-related mortality
Percentage of donor chimerism in patients treated

Secondary Outcome Measures

Full Information

First Posted
December 7, 2001
Last Updated
July 12, 2016
Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00027573
Brief Title
Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Metastatic or Unresectable Kidney Cancer
Official Title
Adoptive Immunotherapy by Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Carcinoma: A Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
October 2001 (undefined)
Primary Completion Date
June 2006 (Actual)
Study Completion Date
June 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alliance for Clinical Trials in Oncology
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer
Keywords
stage IV renal cell cancer, recurrent renal cell cancer, clear cell renal cell carcinoma, papillary renal cell carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy + stem cell transplantation
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Primary Outcome Measure Information:
Title
Overall response rate
Time Frame
Up to 5 years
Title
Overall survival
Time Frame
Up to 5 years
Title
Disease-free survival
Time Frame
Up to 5 years
Title
Treatment-related mortality
Time Frame
Up to 5 years
Title
Percentage of donor chimerism in patients treated
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian I. Rini, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Study Chair
Facility Information:
Facility Name
CCOP - Mayo Clinic Scottsdale Oncology Program
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259-5404
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5289
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
CCOP - Northern New Jersey
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
CCOP - Oklahoma
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16785067
Citation
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.
Results Reference
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Learn more about this trial

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

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