Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer

June 18, 2020 updated by: National Heart, Lung, and Blood Institute (NHLBI)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

156

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • NIH - Warren Grant Magnuson Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA - PATIENT:

Ages 18-80 years.

Biopsy proven metastatic RCC, not amenable to complete surgical resection, progressive bidimensionally evaluable clinically or radiographically.

No prior treatment for RCC within 30 days.

HIV negative.

ECOG performance status of 1 or less.

No major organ dysfunction precluding transplantation.

DLCO greater than or equal to 65% predicted.

Left ventricular ejection fraction greater than or equal to 40%.

HLA 6/6 or 5/6 matched family related donor available.

Ability to comprehend the investigational nature of the study and provide informed consent.

Durable power of attorney signed.

INCLUSION CRITERIA - DONOR:

HLA 6/6 or 5/6 matched family related donor.

Fit to receive G-CSF and give peripheral blood stem cells (normal blood counts, normotensive, no history of stroke).

Ability to comprehend the investigational nature of the study and provide informed consent.

Ages 18-80.

EXCLUSION CRITERIA (any of the following) - PATIENT:

Patient Pregnant.

Age greater than 80 or less than 18 years.

ECOG performance status of 2 or more. Psychiatric disorder or mental deficiency of the patient or donor sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.

Major anticipated illness or organ failure incompatible with survival from BMT where survival is considered insufficient to assess transplant outcome (i.e. less than 3 months).

DLCO less than 65% predicted.

Left ventricular ejection fraction less than 40%.

Serum creatinine greater than 2.5mg/dl or creatinine clearance less than 50 cc/min by 24 hour urine collection.

Serum bilirubin greater than 4 mg/dl, transaminases greater than 3 x upper limit of normal.

HIV positive.

History of other malignancies except basal cell or squamous carcinoma of the skin.

Disease which is limited and amenable to complete surgical resection.

Lack of evidence for progressive disease.

Disease which is not evaluable clinically or radiographically.

Evidence for CNS metastatic disease.

Disease involving greater than 25% of the liver radiographically.

Hypercalcemia (greater than 2.5 mmol/L).

EXCLUSION CRITERIA - DONOR:

Donor pregnant or lactating.

Donor HIV or HBsAg positive.

History of malignancy within 5 years except basal cell or squamous carcinoma of the skin.

Donor unfit to receive G-CSF and undergo apheresis (Uncontrolled hypertension, history of stroke, thrombocytopenia).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
The target for progenitor cell is >=5 x 106 CD 34/kg.
Other: HLA Matched Peripheral BLood Stem Cells
Cell Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The anti-tumor effect of allogenic peripheral blood stem cell transplantation in patients with progressive metastatic renal cell carcinoma.
Time Frame: 5 Years
5 Years

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluate the safety and toxicity of a nonmyeloblative, low intensity, preparative regimen followed by an HLA matched allogenic peripheral blood stem cell transplant in patients with metastatic renal cell carcinoma.
Time Frame: 100 Days
100 Days
The relationship between donor-host chimerism and the incidence of acute and chronic GVHD. The effect of donor lymphocyte infusions on donor-host chimerism. Response rate, disease free and overall survival and mortality.
Time Frame: 100 days
100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Study Chair: Richard W. Childs, MD, National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 9, 1998

Primary Completion (Actual)

June 27, 2011

Study Completion (Actual)

June 27, 2011

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

June 19, 2020

Last Update Submitted That Met QC Criteria

June 18, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 970196
  • NHLBI-97-H-0196
  • CDR0000066610 (Other Identifier: NIH)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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