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

Stage IV Renal Cell Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005851
• Other study ID #: 1495.00
• Secondary ID: NCI-2012-0058114
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2000
• Est. completion date: September 27, 2018

Study information

• Verified date: July 2019
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Description:

PRIMARY OBJECTIVES:

I. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: September 27, 2018
• Est. primary completion date: July 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 74 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Recurrent Renal Cell Cancer
• Stage IV Renal Cell Cancer

Intervention

Drug:
• fludarabine phosphate
Given IV

Radiation:
• total-body irradiation
Undergo TBI

Procedure:
• nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative allogeneic PBSC transplantation

Drug:
• cyclosporine
Given PO or IV
• mycophenolate mofetil
Given PO or IV

Procedure:
• peripheral blood stem cell transplantation
Undergo nonmyeloablative allogeneic PBSC transplantation

Biological:
• therapeutic allogeneic lymphocytes
Undergo DLI

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Baylor University Medical Center	Dallas	Texas
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	VA Puget Sound Health Care System	Seattle	Washington
United States	University of Arizona Health Sciences Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 5 years
Primary	Transplant-related mortality	Defined as death before day 200 not related to progression of disease.	Within 200 days of transplant
Primary	Rate of grade IV acute GVHD		Up to 90 days after last T-cell infusion
Secondary	Survival	Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.	Up to 5 years
Secondary	Incidence of relapse	Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.	Up to 5 years
Secondary	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.	Up to 2 months post-transplant
Secondary	Incidence of aplasia after DLI	Will be examined separately and reported in a descriptive manner and confidence intervals will be presented.	Until 2 months post-transplant
Secondary	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.	Up to 90 days after last T-cell infusion
Secondary	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.	Up to 90 days after last T-cell infusion