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Recurrent Renal Cell CancerPhase 1/2NCT00005851

Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Stage IV Kidney Cancer

A Phase 1/2 study testing fludarabine phosphate, total-body irradiation and nonmyeloablative allogeneic hematopoietic stem cell transplantation in people with Recurrent Renal Cell Cancer and Stage IV Renal Cell Cancer, run by Fred Hutchinson Cancer Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The reason for doing this study is to see if cancer will respond to immune therapy after transplantation of blood stem cells (from the bone marrow) using a new kind of treatment regimen that is less toxic than that previously used for blood stem cell transplants. Read more about this study

Who is it for?
Ages Up to 74 years
What is being tested?
fludarabine phosphate, total-body irradiation and nonmyeloablative allogeneic hematopoietic stem cell transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
6 sitesUnited States
Study dates
Feb 2000to 27 Sep 2018
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 74 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients with histologically confirmed stage IV renal cancer who have stable (including those rendered to be in remission) or progressive disease
  • Human lymphocyte antigen (HLA) genotypically identical related donor willing to undergo leukapheresis initially for collection of peripheral blood stem cells (PBSC) and subsequently for collection of peripheral blood mononuclear cells (PBMC)
  • Ionized calcium level within normal limits
  • DONOR: HLA genotypically identical family member (excluding identical twins)
  • DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
  • DONOR: Age < 75 years

Who cannot join

  • Patients who have positive serologies for human immunodeficiency virus (HIV)1 and 2, human T-lymphotropic virus (HTLV)-1
  • Patients unwilling to use contraceptive techniques during and for 12 months following treatment
  • Serum creatinine > 2.0; the Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC) may approve patients with elevated serum creatinine following presentation and approval; centers outside the FHCRC that have a PCC or equivalent should obtain their institutional approval; if there is not a comparable group at the institution, please contact the FHCRC Principal Investigator for FHCRC approval through PCC
  • Cardiac ejection fraction < 50%; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease
  • Diffusion capacity of carbon monoxide (DLCO) < 50% of predicted, total lung capacity (TLC) < 50%, forced expiratory volume in one second (FEV1) < 50%
  • Liver function tests including total bilirubin, serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) > 2 x the upper limit of normal unless due to the malignancy
Show all 20Show fewer
  • Karnofsky score < 80
  • Brain metastasis
  • Ongoing active bacterial, viral or fungal infection
  • Pregnancy or breastfeeding
  • Patients with other active non-hematologic malignancies (except non-melanoma skin cancers)
  • Patients with a history of other non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
  • The addition of cytotoxic agents for "cytoreduction" with the exception of Gleevec (imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Infection with HIV
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
  • DONOR: Failure to meet criteria for donation as described in the Standard Practice Guidelines of the institution

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Froedtert and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • VA Puget Sound Health Care System

    Seattle, Washington, 98101

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: Phase I/II Study of HLA-Matched Non-Myeloablative Peripheral Blood Mobilized Hematopoietic Progenitor Cell Transplantation as Treatment for Patients With Metastatic Renal Cell Carcinoma. A Multi-Center Trial.

The reason for doing this study is to see if cancer will respond to immune therapy after transplantation of blood stem cells (from the bone marrow) using a new kind of treatment regimen that is less toxic than that previously used for blood stem cell transplants. This type of transplant uses much less chemotherapy and radiation than standard bone marrow transplants. The treatment consists of medications that weaken the immune system so it doesn't reject the donor's marrow cells. Researchers hope that the immune cells from the donor will attack the tumor. This is called a "graft versus tumor" effect and has been seen in other types of cancer. In addition, 65 days or more after the transplant the patient may be eligible for an immune treatment that uses additional immune cells from the donor to increase the effect of the stem cells against the cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether mixed or full donor hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen.

II. To determine whether mixed chimerism can be safely converted to full donor hematopoietic chimerism by infusions of donor lymphocytes (DLI).

III. To evaluate potential efficacy of this approach as a treatment for metastatic renal cancer.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

IMMUNOSUPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV once daily (QD) or BID on days -3 to 35 with taper to day 56, and mycophenolate mofetil PO or IV over 2 hours thrice daily (TID) on days 0-40.

DLI: Patients with stable mixed chimerism on day 56 with no evidence of graft-vs-host disease (GVHD) may receive escalating doses of non-mobilized DLI over 30 minutes. Patients may receive up to 4 DLIs at escalating doses if there is disease progression with no evidence of GVHD.

After completion of study treatment, patients are followed up periodically for 5 years.

Being tested
fludarabine phosphate, total-body irradiation, nonmyeloablative allogeneic hematopoietic stem cell transplantation, cyclosporine, mycophenolate mofetil
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • total-body irradiationRadiation

    Also called TBI

    Undergo TBI

  • nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo nonmyeloablative allogeneic PBSC transplantation

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given PO or IV

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given PO or IV

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo nonmyeloablative allogeneic PBSC transplantation

  • therapeutic allogeneic lymphocytesBiological

    Also called ALLOLYMPH

    Undergo DLI

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00005851
Study groupRoleWhat they receive
Treatment (nonmyeloablative donor PBSC transplantation)ExperimentalCONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. IMMUNOSUPRESSION: Patients receive cyclosporine PO BID or IV QD or BID on days -3 to 35 with taper to day 56, and mycophenolate mofetil PO or IV over 2 hours TID on days 0-40. DLI: Patients with stable mixed chimerism on day 56 with no evidence of GVHD may receive escalating doses of non-mobilized DLI over 30 minutes. Patients may receive up to 4 DLIs at escalating doses if there is disease progression with no evidence of GVHD.
Receives: Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Drug: cyclosporine; Drug: mycophenolate mofetil; Procedure: peripheral blood stem cell transplantation; Biological: therapeutic allogeneic lymphocytes; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. True response rate (complete response [CR] or partial response [PR]) greater than the 15% achievable with standard therapy

    If 6 or more out of 25 patients achieve a CR or PR, then there is at least 80% confidence that the true response rate exceeds 15% and that this approach is potentially efficacious.

    Measured: Up to 5 years

  2. Transplant-related mortality

    Defined as death before day 200 not related to progression of disease.

    Measured: Within 200 days of transplant

  3. Rate of grade IV acute GVHD

    Measured: Up to 90 days after last T-cell infusion

Secondary outcomes (6)

  1. Survival

    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.

    Measured: Up to 5 years

  2. Incidence of relapse

    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.

    Measured: Up to 5 years

  3. Incidence of myelosuppression after initial PBSC infusion

    Defined as absolute neutrophil count < 500 for > 2 days, platelets < 20,000 for > 2 days. Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.

    Measured: Up to 2 months post-transplant

  4. Incidence of aplasia after DLI

    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.

    Measured: Until 2 months post-transplant

  5. Incidence of grades 2-4 acute GVHD after DLI

    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.

    Measured: Up to 90 days after last T-cell infusion

  6. Incidence of grades chronic extensive GVHD after DLI

    Will be examined separately and reported in a descriptive manner and confidence intervals will be presented for all estimates.

    Measured: Up to 90 days after last T-cell infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startFeb 2000
  3. Primary completionJul 2004
  4. Study completion27 Sep 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00005851
Sponsor's protocol ID
1495.00
Other IDs
NCI-2012-00581, 1495.00, P30CA015704
Status last verified
Jul 2019
First submitted
2 Jun 2000
Last updated
24 Jul 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing fludarabine phosphate, total-body irradiation and nonmyeloablative allogeneic hematopoietic stem cell transplantation in people with Recurrent Renal Cell Cancer and Stage IV Renal Cell Cancer, run by Fred Hutchinson Cancer Center at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

True response rate (complete response [CR] or partial response [PR]) greater than the 15% achievable with standard therapy (time frame: Up to 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00005851.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2019.

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