Pentostatin and Cyclophosphamide Followed By Donor Stem Cell Transplant and Donor Lymphocyte Infusions in Patients With Metastatic Kidney Cancer

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

Status: Recruiting

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

Secondary outcome:

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

Detailed description: OBJECTIVES:

Primary

- 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.

Secondary

- 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

transplant regimen.

- 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

22-84.

- 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. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

- 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

involvement)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 1 year after

transplantation

- 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

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