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

NCT00005851 | Completed Phase 1 DMC

• 3 other identifiers: 1495.00NCI-2012-00581P30CA015704
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Recurrent Renal Cell Cancer; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (3)

• 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

• Transplant-related mortality

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

  Within 200 days of transplant

• Rate of grade IV acute GVHD

  Up to 90 days after last T-cell infusion

Secondary Outcomes (6)

• Survival

  Up to 5 years

• Incidence of relapse

  Up to 5 years

• Incidence of myelosuppression after initial PBSC infusion

  Up to 2 months post-transplant

• Incidence of aplasia after DLI

  Until 2 months post-transplant

• Incidence of grades 2-4 acute GVHD after DLI

  Up to 90 days after last T-cell infusion

Study Arms (1)

Treatment (nonmyeloablative donor PBSC transplantation)

EXPERIMENTAL

CONDITIONING 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.

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

Interventions

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (nonmyeloablative donor PBSC transplantation)

total-body irradiation RADIATION

Undergo TBI

Also known as: TBI

Treatment (nonmyeloablative donor PBSC transplantation)

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplantation

Treatment (nonmyeloablative donor PBSC transplantation)

cyclosporine DRUG

Given PO or IV

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Treatment (nonmyeloablative donor PBSC transplantation)

mycophenolate mofetil DRUG

Given PO or IV

Also known as: Cellcept, MMF

Treatment (nonmyeloablative donor PBSC transplantation)

peripheral blood stem cell transplantation PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplantation

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (nonmyeloablative donor PBSC transplantation)

therapeutic allogeneic lymphocytes BIOLOGICAL

Undergo DLI

Also known as: ALLOLYMPH

Treatment (nonmyeloablative donor PBSC transplantation)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (nonmyeloablative donor PBSC transplantation)

Eligibility Criteria

• Age: Up to 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Rocky Mountain Cancer Centers-Aurora

Aurora, Colorado, 80012, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98101, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

fludarabine phosphate; Whole-Body Irradiation; Cyclosporine; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Study Officials

• Brenda Sandmaier

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2000
• First Posted: January 27, 2003
• Study Start: February 1, 2000
• Primary Completion: July 1, 2004
• Study Completion: September 27, 2018
• Last Updated: July 24, 2019

Record last verified: 2019-07

Locations

US (6)