Low-Intensity Stem Cell Transplantation With Multiple Lymphocyte Infusions to Treat Advanced Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00923845
First received: June 17, 2009
Last updated: June 26, 2014
Last verified: November 2013
  Purpose

Background:

Low-dose chemotherapy is easier for the body to tolerate than typical high-dose chemotherapy and involves a shorter period of complete immune suppression.

Donor immune cells called lymphocytes, or T cells, fight residual tumor cells that might have remained in the recipient s body after stem cell transplant, in what is called a graft-versus-tumor (GVT) effect.

The immune-suppressing drug sirolimus appears to help prevent graft-versus-host disease (GVHD), a side effect of stem cell transplant in which donated T cells sometimes attack healthy tissues, damaging organs such as the liver, intestines and skin.

Th2 cells are cells collected from the transplant donor and grown in a high concentration of sirolimus.

Objectives:

To determine whether stem cell transplantation using low-dose chemotherapy and sirolimus-generated Th2 cells can cause a remission of advanced kidney cancer.

Eligibility:

Patients between 18 and 75 years of age who have kidney cancer that has spread beyond the kidney and who have a tissue-matched sibling stem cell donor.

Design:

Patients undergo stem cell transplantation as follows:

  • Low-intensity chemotherapy with pentostatin and cyclophosphamide over a 21-day period to reduce the level of the immune system to prepare for the transplant. Pentostatin is given through a vein (IV) on days 1, 8 and 15; cyclophosphamide tablets are taken by mouth for 21 consecutive days.
  • Sirolimus tablets, taken by mouth, starting 2 days before the transplant and continuing until 60 days after the transplant.
  • IV infusions of stem cells and Th2 cells.

Following the transplant, patients have the following procedures:

  • Additional Th2 cell infusions on days 14 and 45 after the transplant.
  • Follow-up visits at the NIH Clinical Center twice a week for the first 6 months after the transplant and then less frequently for at least 5 years to evaluate response to treatment and treatment side effects. Evaluations include a bone marrow aspirate and biopsy 1 month after transplant and periodic blood tests and imaging procedures (e.g., CT or MRI scans).

Condition Intervention Phase
Renal Cell Carcinoma
Graft-Versus-Host Disease
Engraftment Syndrome
Drug: Pentostatin
Drug: Sirolimus
Drug: Cyclophosphamide
Procedure: Allogeneic Hematopoietic Stem Cell Transplant
Procedure: Th2 Cell Transplantation
Drug: Th2 Cells in Allogeneic HSCT
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The primary outcome will be the frequency of subjects that achieve a partial remission of tumor (PR) or complete remission of tumor (CR). Tumor response will be measured by the RECIST criteria.

Secondary Outcome Measures:
  • (1) Immune depleting effect of pentostatin + cyclophosphamide; (2) Characterize the pattern of alloengraftment observed after this low-intensity transplant approach; (3) Evaluate any anti-tumor effector mechanism.

Estimated Enrollment: 54
Study Start Date: March 2008
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Pentostatin
    N/A
    Drug: Sirolimus
    N/A
    Drug: Cyclophosphamide
    N/A
    Procedure: Allogeneic Hematopoietic Stem Cell Transplant
    N/A
    Procedure: Th2 Cell Transplantation
    N/A
    Drug: Th2 Cells in Allogeneic HSCT
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA: Recipient

Diagnosis of metastatic renal cell carcinoma, either clear cell type or non-clear cell type. The diagnosis must be confirmed by the Laboratory of Pathology of NCI or Hackensack (there will be no central pathology review).

The consent process will include a discussion of the potential role of high-dose IL-2 therapy prior to protocol enrollment. High-dose IL-2 therapy is not widely available, but may be available on an NCI protocol (Dr. Yang) or through Dr. Alter for Hackensack patients. IL-2 therapy may also be administered by any other qualified physician; the Novartis web-site has a list of such physicians. For subjects who are deemed to be eligible for high-dose IL-2 and elect to receive this therapy, such subjects must have progressive disease post-IL-2 to enter this study; such subjects must also have received and have had progressive disease after therapy with one of the agents listed below.

Subject must have progressive disease after therapy consisting of one of the following FDA-approved agents: sorafenib, sunitib, or temsirolimus.

Patients 18 - 75 years of age. Subjects older than 75 will not be enrolled due to an increased rate of transplant-related complications.

Must have consenting sibling matched at 6/6 HLA antigens (A, B, DR).

Patient or legal guardian must be able to give informed consent.

All previous therapy must be completed at least 2 weeks prior to study entry. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less.

Karnofsky performance status greater than or equal to 80%.

Life expectancy of at least 3 months.

Left ventricular ejection fraction greater than 40% (MUGA or echo) within 28 days of enrollment.

DLCO greater than 50% of expected value (Hb corrected), obtained within 28 days of enrollment.

Creatinine clearance greater than or equal to 40 ml/min. Creatinine clearance will be determined by testing of a 24 hour urine collection and simultaneous serum creatinine value. In previous studies, the creatine clearance of patients with metastatic renal cell cancer who underwent nephrectomy was 53 plus or minus 19.

Serum total bilirubin less than 2.5 mg/dl, and serum ALT and AST values less than or equal to 2.5 times the upper limit of normal. ALT and AST values above these levels may be accepted (up to a maximum of 5 times the upper limit of normal), at the discretion of the PI or study chairperson, if such elevations are thought to be due to liver involvement by malignancy.

INCLUSION CRITERIA : Donor

Sibling who is 6/6 HLA-matched with recipient.

Ability to give informed consent.

Age 18 years to 80 years. Donors older than 80 will not be eligible due to potentially increased complications from the donation procedure.

Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis.

Donors must be HIV negative, hepatitis B surface antigen negative, and hepatitis C antibody negative. This is to prevent the possible transmission of these infections to the recipient. Donors with a history of hepatitis B or hepatitis C infections may be eligible. However, eligibility determination of such patients will require a hepatology consultation. The risk/benefit of the transplant and the possibility of transmitting hepatitis will be discussed with the patient and eligibility will then be determined by the principal investigator.

A donor who is lactating must substitute formula feeding for her infant during the period of cytokine administration. Filgrastim may be secreted in human milk, although its bioavailability from this source is not known. Limited clinical data suggest that administration of filgrastim or to neonates is not associated with adverse outcomes.

EXCLUSION CRITERIA: Recipient

Active infection that is not responding to antimicrobial therapy.

Active CNS involvement by malignancy.

HIV infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.

Chronic active hepatitis B. Patient may be hepatitis B core antibody positive. For patients with concomitant positive hepatitis B surface antigen, patient will require a hepatology consultation. The risk/benefit profile of transplant and hepatitis B will be discussed with the patient and eligibility determined by the principal investigator and protocol chairperson.

Hepatitis C infection. Patient may have hepatitis C infection. However, each patient will require a hepatology consultation. The risk/benefit profile of transplant and hepatitis C will be discussed with the patient and eligibility determined by the principal investigator and protocol chairperson.

Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception from the time of study entry to at least one year post-transplant; effective methods include intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation/hysterectomy, partner s vasectomy, or barrier methods (condom, diaphragm, or cervical cap). Males on the protocol, and their partners of child-bearing potential, must also use an effective form of contraception at study entry and for one year post-transplant. The effects of the chemotherapy, the subsequent transplant, and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant; therefore, women should not breastfeed during the interval from study entry to one year post-transplant.

History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent (as determined by principal investigator or study chairman).

EXCLUSION CRITERIA: Donor

History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.

History of hypertension that is not controlled by medication, stroke, or severe heart disease. Individuals with symptomatic angina will be considered to have severe heart disease and will not be eligible to be a donor.

No other medical contraindications to stem cell donation (i.e. severe atherosclerosis, autoimmune disease, iritis or episcleritis, deep venous thrombosis, cerebrovascular accident). Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.

History of prior malignancy. However, cancer survivors who have undergone potentially curative therapy may be considered for stem cell donation on a case-by-case basis. The risk/benefit of the transplant and the possibility of transmitting viable tumor cells at the time of transplantation will be discussed with the patient.

Donors must not be pregnant. The effects of cytokine therapy on a fetus are unknown. Donors of childbearing potential must use an effective method of contraception from the time of study entry until at least one year post-transplant.

Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000 per microliter).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00923845

Contacts
Contact: Zetta A Blacklock-Schuver, R.N. (301) 451-6569 bblacklock@mail.nih.gov
Contact: Daniel H Fowler, M.D. (301) 402-8641 dhfowler@helix.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Daniel H Fowler, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00923845     History of Changes
Obsolete Identifiers: NCT00641485
Other Study ID Numbers: 080088, 08-C-0088
Study First Received: June 17, 2009
Last Updated: June 26, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Metastatic Renal Cell Carcinoma
Allogeneic Hematopoietic Stem Cell Transplant
Th2 Cells
Sirolimus
Pentostatin
Kidney Cancer
Renal Cell Carcinoma
Metastatic Renal Cell Cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Carcinoma
Graft vs Host Disease
Adenocarcinoma
Immune System Diseases
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Cyclophosphamide
Everolimus
Pentostatin
Sirolimus
Adenosine Deaminase Inhibitors
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 23, 2014