Pentostatin and Cyclophosphamide Followed By Donor Stem Cell Transplant and Donor Lymphocyte Infusions in Patients With Metastatic Kidney Cancer
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Kidney Cancer
Intervention: therapeutic allogeneic lymphocytes (Biological); cyclophosphamide (Drug); pentostatin (Drug); sirolimus (Drug); allogeneic hematopoietic stem cell transplantation (Procedure); peripheral blood stem cell transplantation (Procedure)
Phase: Phase 2
Sponsored by: National Cancer Institute (NCI)
Official(s) and/or principal investigator(s):
Daniel Fowler, MD, Principal Investigator, Affiliation: National Cancer Institute (NCI)
RATIONALE: Giving low doses of chemotherapy, such as pentostatin and cyclophosphamide, before
a donor stem cell transplant helps stop the growth of tumor cells. It also stops 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
sirolimus before and after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving pentostatin together with
cyclophosphamide followed by donor stem cell transplant and donor lymphocyte infusion works
in treating patients with metastatic kidney cancer.
Official title: Low Intensity Allogeneic Hematopoietic Stem Cell Transplantation Therapy of Metastatic Renal Cell Carcinoma Using Early and Multiple Donor Lymphocyte Infusions Consisting of Sirolimus-Generated Donor Th2 Cells
Study design: Treatment
Primary outcome: Achievement of clinical regression based on a 40% overall partial or complete response rate
Safety of pentostatin and cyclophosphamide
Immune-depleting and immune-suppressive effects of pentostatin and cyclophosphamide
Engraftment kinetics and graft-versus-host disease profile
Post-transplant immunity, including cytokine phenotype, immune reconstitution, and potential anti-tumor effector mechanisms
- Determine whether treatment with low-intensity chemotherapy comprising pentostatin and
cyclophosphamide followed by allogeneic hematopoietic stem cell transplantation and
donor Th2 cell infusions results in clinical tumor regression (with the goal of ruling
out a 20% overall partial response(PR)/complete response (CR) rate in favor of a 40%
PR/CR rate) in patients with metastatic renal cell carcinoma.
- To characterize the safety and immune-depleting and immune-suppressive effects of
pentostatin and cyclophosphamide.
- To characterize the engraftment kinetics and graft-versus-host disease profile of this
- To characterize post-transplant immunity, including cytokine phenotype, immune
reconstitution, and potential anti-tumor effector mechanisms.
OUTLINE: This is a multicenter study.
- Induction therapy: Patients receive oral cyclophosphamide once daily on days 1-21 and
pentostatin IV on days 1, 8, and 15.
- Allogeneic hematopoietic stem cell transplantation: Patients receive allogeneic
peripheral blood stem cells IV on day 24.
- Graft-versus-host disease prophylaxis: Patients receive high-dose oral sirolimus on days
- Donor lymphocyte infusions: Patients receive donor Th2 cells IV on days 24, 38, and 69.
After completion of therapy, patients are followed periodically for at least 5 years.
Minimum age: 18 Years.
Maximum age: 75 Years.
- Diagnosis of metastatic renal cell carcinoma
- Clear cell type or non-clear cell type
- Has undergone prior nephrectomy (either partial or complete resection)
- Progressive disease after prior treatment with sorafenib, sunitinib, or temsirolimus
- Patients who are eligible for high-dose interleukin-2 (IL-2) and elect to receive this
therapy must have progressive disease after treatment with IL-2 AND must also have
progressive disease after treatment with sorafenib, sunitinib, or temsirolimus
- No active CNS involvement by malignancy
- 6/6 HLA-matched (A, B, DR) sibling donor available
- Karnofsky performance status 80-100%
- Life expectancy ≥ 3 months
- Left ventricular ejection fraction > 40% by MUGA or ECHO
- DLCO > 50% of expected value (hemoglobin corrected)
- Creatinine clearance ≥ 40 mL/min
- Total bilirubin < 2. 5 mg/dL
- Serum ALT and AST ≤ 2. 5 times upper limit of normal (ULN) (5 times ULN if due to liver
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 1 year after
- No active infection that does not respond to antimicrobial therapy
- No HIV infection
- No chronic active hepatitis B
- Hepatitis B core antibody positive allowed
- No history of psychiatric disorder that would preclude compliance with study or that
would preclude giving informed consent
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Locations and Contacts
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office, Bethesda, Maryland 20892-1182, United States; Recruiting
Clinical Trials Office - Warren Grant Magnusen Clinical Center, Phone: 888-NCI-1937
Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States; Recruiting
Clinical Trials Office - Hackensack University Medical Center, Phone: 201-996-2879
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: March 2008
Last updated: February 6, 2009