Clinical Trial Detail

Clinical Trials

Clinical Trial Detail

Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

Complete title: A Phase II Study Evaluating Selective Depletion of CD45RA+ T Cells from Allogeneic Peripheral Blood Stem Cell Grafts from HLA-Matched Related and Unrelated Donors for Prevention of GVHD

Research Study Number 2684.00
 
Principal Investigator Marie Bleakley, MD
 
Phase II

Research Study Description

This phase II trial studies how well selective T cell depletion works in preventing graft-versus-host disease (GVHD) in patients with acute lymphocytic leukemia, acute myeloid leukemia, or chronic myelogenous leukemia undergoing donor peripheral blood stem cell transplant. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing a subset of the T cells from the donor cells before transplant may stop this from happening.

Eligibility Criteria (must meet the following to participate in this study)

Ages Eligible for Study: 14 Years to 60 Years (Child, Adult)

Sexes Eligible for Study: All

- Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:

-- * Acute lymphocytic leukemia in first or subsequent remission

-- * Acute myeloid leukemia in first or subsequent remission

-- * Acute lymphocytic leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 (Arms A or C only)

-- * Acute myeloid leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 (Arms A or C only)

-- * Refractory anemia with excess blasts (RAEB-1 and RAEB-2) (if the patient has received previous induction chemotherapy within 60 days)

-- * Chronic myelogenous leukemia with a history of accelerated phase or blast crisis (if the patient has received at least one course of induction chemotherapy)

-- * Other acute leukemia or related neoplasm (including but not limited to 'biphenotypic', 'undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm or lymphoblastic lymphoma)

- Patients 14-49 years old will be enrolled in Arm A or C (high-intensity)

- Patients 50-60 years old will be enrolled in Arm B or D (lower intensity); patients eligible for Arms B or D also include those who have received previous allogeneic HCT, or who have co-morbid conditions rendering them unsuitable for high-dose conditioning, determined in consultation with the principal investigator

- Patient with a HLA-matched (HLA-A, B, C, and DR beta 1 [DRB1] molecularly matched) unrelated donor or related donor capable of donating PBSC

DONOR INCLUSION:

- HLA-matched related donors >= 18 years and capable and willing to donate PBSC (Arms A and B)

- HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution typing) capable and willing to donate PBSC (Arms C and D)

Other eligibility criteria may apply.

Exclusions (conditions that would prevent participation in this study)

- Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation

- Patients on other experimental protocols for prevention of acute GVHD

- Patient weight >= 100 kg; patients >= 70 kg with MUDs must be discussed with the principal investigator

- Patients who are human immunodeficiency virus positive (HIV+)

- Patients with uncontrolled infections for whom myeloablative HCT is considered contraindicated by the consulting infectious disease physician (upper respiratory tract viral infection does not constitute an uncontrolled infection in this context)

- Patients with organ dysfunction

ARM A OR C EXCLUSION:

- Creatinine > 1.5 mg/dl at the present time; patients with a known history of creatinine > 1.5 mg/dl must have a current estimated creatinine clearance of > 40 ml/min

- Cardiac ejection fraction < 45%

- Diffusing capacity of the lung for carbon monoxide (DLCO) corrected < 60%

- Liver function abnormality; patients who have liver function tests (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal should be evaluated by a gastrointestinal (GI) physician; unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); if the GI physician considers that HCT on the high-intensity arms of protocol is contraindicated for that patient the patient may be considered for treatment on the lower intensity arm of the protocol or excluded from the protocol; patients with Gilbert's syndrome and no other known liver function abnormality and patients with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the high-intensity arms of the protocol

ARM B OR D EXCLUSION:

- Creatinine > 2.0 mg/dl at the present time; patients with a known history of creatinine > 1.5 mg/dl must have a current estimated creatinine clearance > 40 ml/min

- Cardiac ejection fraction < 35%

- DLCO corrected < 50%; patients with a DLCO 50-60% must also have a partial pressure of oxygen (pO2) of > 80 mmHg

- Liver function abnormality; patients who have LFTs >= twice the upper limit of normal should be evaluated by a GI physician; unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded

- Patients will be excluded from Arms A and C if they have received a previous myeloablative transplant; patients who have received a prior HCT at least 6 months prior may be considered for inclusion on Arms B or D after discussion with the principal investigator (PI)

- Patients with a life expectancy < 3 months from co-existing disease other than the leukemia or RAEB

- Patients who are pregnant or breast-feeding

- Fertile patients of child bearing age unwilling to use contraception during and for 12 months post-transplant

- Patients with a significant other medical conditions that would make them unsuitable for transplant

- Patients with a known hypersensitivity to tacrolimus, methotrexate (Arm A or C) or MMF (Arm B or D)

DONOR EXCLUSION:

- Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection

- Donors who fail eligibility requirements for donation of cells or tissue for donation of a Human Cell and Tissue Products (HCT/P) will be excluded unless use of the cells complies urgent medical need or allogeneic use in a first-degree or second-degree relative

- Unrelated donors donating outside of the United States of America (USA)

Other exclusion criteria may apply.

Research Study Number 2684.00
 
Contact Seattle Cancer Care Alliance Intake Office
 
Telephone 800-804-8824 / 206-606-1024
 

Keywords: Leukemia, Acute Lymphoblastic (ALL); Leukemia, Acute Myeloid (AML); Hematologic Malignancies; Leukemia; Lymphoproliferative Disorders; Pediatric Cancers, Miscellaneous; Myelodysplastic Syndromes (MDS); Graft Versus Host Disease, Chronic (cGVHD); Graft Versus Host Disease (GVHD); Leukemia, Myeloid; Leukemia, Lymphoid; Immunoproliferative Disorders; Myeloproliferative Disorders (MPD); Anemia; Bone Marrow Diseases; Immunotherapy

Disclaimer: We update this information regularly. However, what you read today may not be completely up to date.

Please remember:

  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.

Subscribe to an RSS feed of all trials