Protocol Number: 01-C-0125

Title:

Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies

Number:

01-C-0125

Summary:

This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating various leukemias and lymphomas in children.

Transplantation of donated stem cells (cells produced by the bone marrow that mature into white and red blood cells and platelets) is a very effective treatment for patients with leukemia, pre-leukemia and lymphoma. However, despite its success in a large number of patients, this procedure has many serious side effects and carries a significant risk of death. These complications result from the intensive chemotherapy and radiation patients receive before the transplant to rid the body of cancer cells. In this study, radiation will not be used and chemotherapy drugs will be given in lower doses to try to reduce the dangers of the procedure.

Patients between 5 and 21 years of age with acute lymphocytic leukemia, acute myelogenous leukemia, myelodysplasia, chronic myelogenous leukemia, juvenile chronic myelogenous or myelomonocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests (including testing for genetic match with the donor), breathing tests, X-rays, scans and other tests to determine eligibility. They may also undergo bone marrow aspiration, in which the hip area is anesthetized and a small sample of bone marrow is drawn through a needle inserted into the hipbone. A spinal tap may be done to look for cancer cells in the central nervous system. This procedure involves numbing the back and inserting a needle between the bones of the spine to withdraw a small amount of spinal fluid. A central venous catheter (flexible plastic tube placed in a vein) will be put in place before treatment begins. It will be used to draw and transfuse blood, give medications, and infuse the donated stem cells.

Before the transplant procedure, patients will receive induction chemotherapy with cyclophosphamide, fludarabine, etoposide, doxorubicin, vincristine and prednisone for 4 days, followed by a 17-day rest period. No more than 3 cycles of this chemotherapy will be given. Following the induction chemotherapy, patients will be admitted to the Clinical Center for 4 days of chemotherapy with cyclophosphamide and fludarabine. The donated stem cells will be infused 3 days later.

Patients can leave the hospital when their white cell counts return to near normal and they have no serious complications. After discharge, they will be followed closely (at least once or twice weekly for the first 100 days after transplant) with a physical exam and blood tests. Patients may require immunoglobulin or antibiotics to fight infections and transfusions of red blood cells and platelets. After the 100 days, follow-up visits will continue less frequently for at least 5 years.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA PATIENTS:

Patients with the following diagnoses will be considered:

-Hodgkin's and Non-Hodgkin's Lymphoma: Refractory (non-CR) to primary treatment regimen; Refractory (non-CR) to or relapse after salvage regimen.

-Acute Myelogenous Leukemia (AML): History of bone marrow relapse it CR number 2 or greater.

-Acute Lymphocytic Leukemia (ALL): History of bone marrow relapse in CR number 2 or greater; complete remission #1 with Philadelphia chromosome positive or prior induction failure (subsequent induction regimen required to achieve CR).

-Acute hybrid leukemia including mixed lineage, biphenotypic, and undifferentiated (AUL): History of bone marrow relapse in CR number 2 or greater; Complete remission #1 with Philadelphia chromosome positive or prior induction failure (second induction regimen required to achieve (CR).

-Myelodysplastic Syndrome (MDS) excluding refractory anemia (RA) and RA with ringed sideroblasts (RARS): blasts less than 10% in marrow and blood.

-Chronic Myelogenous Leukemia (CML): Chronic Phase; Accelerated Phase with blasts less than 10% in marrow and blood.

-Juvenile Myelomonocytic Leukemia (JMML, J-CML) : Blasts less than 10% in marrow and blood.

Patients must be greater than or equal to 4 years and less than 22 years of age.

Prior chemotherapy: Chemotherapy to achieve above noted criteria allowed. Prior autologous BMT allowed. Prior allogeneic BMT allowed as long as at least day +100 post-prior BMT, and no evidence of ongoing active GVHD.

Availability of 5 or 6 antigen genotypic HLA-matched first-degree relative donor (single HLA-A or B locus mismatch allowed).

Performance status of 0,1,or 2.

Life expectancy greater than 3 months.

Liver function: serum direct bilirubin less than 2.0 mg/dL, and serum ALT and AST values less than or equal to 2.5 times the upper limit of normal. Values above these levels may be accepted, at the discretion of the PI, if such elevations are thought to be due to malignancy (excluding acute leukemia).

Renal function: age-adjusted normal serum creatinine or a creatinine clearance greater than or equal to 60 mL/min/1.73 m(2).

Pulmonary function: DLCO corrected for hemoglobin and alveolar volume greater than or equal to 50% of predicted.

Left ventricular function: Ejection fraction greater than or equal to 45% by MUGA or shortening fraction greater than or equal to 28% by ECHO.

Ability to give informed consent. For patients less than 18 years old their legal guardian must give informed consent. Pediatric patients will be included in age appropriate discussion in order to obtain verbal assent.

Durable power of attorney form completed (patients greater than 18 years of age only).

Patients must not have an active CNS malignancy as defined by: lymphoma (tumor mass on CT scan or leptomeningeal disease), Leukemia (CNS 2 or CNS 3 classification), or NB (History of CNS involvement with no current evidence of CNS malignancy is NOT an exclusion).

Patients must not be HIV positive.

Patients must not have active hepatitis B or C infection as defined by seropositive for hepatitis B (HbSAg) or hepatitis C and elevated liver transaminases.

Female patients must not be lactating or pregnant (due to risk to fetus or newborn).

Patients must not have high risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team.

Patients must not have Fanconi Anemia (FA): patients with MDS must have a negative FA test.

INCLUSION CRITERIA DONOR:

First degree relative with genotypic identity at 5 or 6 HLA loci (single HLA-A or B locus mismatch allowed).

Weight of greater than or equal to 15 kilograms.

Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis (on Cohort #2, for possible future cell collection if needed).

Ability to give informed consent. For donors less than 18 years of age, he/she must be the oldest eligible donor, their legal guardian must give informed consent, the donor must give verbal assent, and he/she must be cleared by social work and a mental health specialist to participate.

Donor selection criteria will be in accordance with NIH/CC Department of Transfusion Medicine standards.

EXLCUSION CRITERIA PATIENT:

Active CNS malignancy as defined by:

-Lymphoma: tumor mass on CT scan or leptomeningeal disease

-Leukemia: CNS 2 or CNS 3 classification

-NB: History of CNS involvement with no current evidence of CNS malignancy is NOT an exclusion.

HIV positive.

Active hepatitis B or C infection as defined by seropositive for hepatitis B (HbsAg) or hepatitis C and elevated liver transaminases.

Lactating or pregnant females.

High risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team.

Fanconi Anemia (FA): Patients with MDS must have a negative FA test.

EXCLUSION CRITERIA DONOR:

History of medical illness which in the estimation of the PI or DTM physician poses prohibitive risk to donation including, but not limited to stroke, hypertension that is not controlled by medication, or heart disease. Individuals with symptomatic angina or a history of coronary artery bypass grafting or angioplasy will not be eligible. History of congenital hematologic, immunologic, or metabolic disorder which in the estimation of the PI poses prohibitive risk to the receipient.

Anemia (Hb less than gm/dl) or thrombocytopenia (less than 100,000/ul).

Lactating or pregnant females.

HIV positive.

Seropositive for hepatitis B (HbsAg) or hepatitis C.

High risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team.

Special Instructions:

Currently Not Provided

Keywords:

Leukemia

Myelodysplastic Syndrome

Bone Marrow Transplant

Pediatric Oncology

Lymphoma

Recruitment Keyword(s):

Childhood Cancer

Bone Marrow Transplant

Condition(s):

Hodgkin Lymphoma

Lymphocytic Leukemia

Mixed Cell Leukemia

Myelodysplastic Syndrome

Non Hodgkin's Lymphoma

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Procedure/Surgery: Stem cell transplantation

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Chronic myelogenous leukemia: A concise update

Acute lymphoblastic leukemia

Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 01/13/2009