Active clinical trials for "Leukemia"

In this trial, the investigators will test the combination of escalating doses of chemotherapy (starting at relatively low dose) with lenalidomide in intermediate-2-or high risk MDS and AML with del 5 q31. It is hoped that this combined therapy will further increase response rate in intermediate-2-or high risk MDS and AML with del 5 q31, without major toxicity in comparison to historical results obtained with chemotherapy alone in the same subset of patients.

The current understanding of PR104 justifies the evaluation of PR104 in subjects with relapsed/refractory AML and ALL. These include: Hypoxia. Leukemic bone marrow is likely to demonstrate a level of hypoxia sufficient to activate PR104 to its active metabolites PR104H and PR104M. Myelotoxicity as the primary toxicity at MTD. In prior clinical studies in subjects with solid tumors PR104 has demonstrated myelotoxicity as the primary toxicity. This observation suggests that PR104 will exert a similar effect on leukemic cells. AKR1C3. AML has been reported to exhibit high levels of AKR1C3 which should lead to selective activation of PR104 within both hypoxic and oxic leukemic cells. Preclinical data. PR104 has demonstrated impressive activity in an initial study using primary human ALL in a mouse model. The initial dose finding phase of the study will provide estimates of the activity and toxicity of PR104 in subjects with refractory/relapsed AML, and determine the optimal individualized dose to give each subject based on his/her covariates (prior CR duration, prior number of salvage therapies, age). Once a potentially beneficial dose has been determined, an expanded cohort of subjects with AML or ALL will receive PR104 at a uniform dose. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity and acceptable safety in AML to warrant future phase II or phase III studies in this indication. Primary objectives Determine the toxicities and recommended dose of PR104 when administered IV to subjects with relapsed/refractory AML and ALL. Secondary objectives Evaluate the pharmacokinetics (PK) of PR104 and a series of PR104 metabolites Evaluate any anti-tumor effects of PR104 Evaluate the expression of AKR1C3 in bone marrow and leukemic cells Evaluate potential biomarkers of hypoxia

There is very limited data on the use of arsenic trioxide in newly diagnosed patients with acute promyelocytic leukemia. The use of arsenic trioxide was limited to relapsed patients mainly because of the superior efficacy of ATRA as primary therapy for newly diagnosed APML. Though the early study by Niu et al showed 72% remission rates in 11 newly diagnosed patients, the role of arsenic trioxide as primary therapy was limited by the hepatic toxicity seen in this study. Studies from our centre have shown remission rates of 70-75% in newly diagnosed patients with acute promyelocytic leukemia. There was no major toxicity seen related to the administration of arsenic trioxide. Follow up data on these patients continue to show long term remission rates above 70%. These remission rates are similar to the data available in patients with acute promyelocytic leukemia treated with ATRA. Lu et al studied 19 patients treated with oral arsenic (Tetra-arsenic tetra-sulfide) wherein 84% achieved hematological remission with disease free survival of 76% at 3 years. Studies from other groups using arsenic trioxide alone or in combination with ATRA have shown similar remission rates. Arsenic trioxide as primary therapy for patients with newly diagnosed acute promyelocytic leukemia is a very attractive treatment option for developing countries mainly because of the low cost involved along with the favorable toxicity profile. However long term remission data is still not available and the ideal course and duration of treatment still needs to be defined. This multi-center study aims to further clarify the efficacy of this agent in the treatment of newly diagnosed cases of acute promyelocytic leukemia and to study the optimal maintenance regimen.

RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming normal cells. This may be an effective treatment for hairy cell leukemia(HCL) that has not responded to chemotherapy, surgery or radiation therapy. PURPOSE: Phase I dose escalation study to determine the maximum tolerated dose of CAT-8015 immunotoxin in treating patients who have hairy cell leukemia (HCL) that has not responded to treatment.

The main purpose of this study is to explore the therapeutic effect of CD20-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of B cell malignancies.

The purpose of this study is to evaluate the efficacy of tyrosine kinase inhibitor(TKI) therapy based on molecular monitoring of BCR/ABL levels in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).

Acute lymphoblastic leukemia (ALL) accounts for 30 % of all childhood malignancies. The patients undergo four phases of treatment, finishing with a late maintenance phase in which 6-mercaptopurine and Methotrexate are essential components. Insufficient treatment intensity in this phase is associated with increased risk of relapse. Excessive variation in the bioavailability of 6-mercaptopurine has been observed which can cause both risks of undertreatment/relapse as well as overtreatment with severe side effects. In the attempt to achieve individualized 6-mercaptopurine dosing different approaches have been pursued. Nonetheless variation in bioavailability remains a problem. Earlier, oral tablets of 50 mg (Purinethol) were the only administration form of 6-mercaptopurine and it was primarily designed for adult patients. Challenges with accurate dosing and getting the children to swallow the tablets have been a widespread problem, forcing the caregivers to divide or crush the tablets as well as having to administer different dosages over 2-3 days. Due to these problems, an oral liquid formulation of 6-mercaptopurine (Xaluprine) has been developed. However this oral liquid has only been tested on healthy adult volunteers, and not on the target group, childhood patients. This project will assess the bioavailability and plasma kinetics of oral liquid and tablet formulation of 6-mercaptopurine in children with acute lymphoblastic leukemia. The investigators hypothesize to observe comparable plasma kinetics, in children with acute lymphoblastic leukemia when treated with 6-mercaptopurine in the form of a tablet and oral liquid formulation, as previously observed in healthy adults.

Allogeneic hematopoietic cell transplantation(Allo-HSCT) is currently an effective treatment for Acute leukemia (AL). Relapse after transplantation, being a main obstacle for patient survival, is so far treated by second transplantation and donor leukocyte infusion (DLI), which seems to have high risk and low survival. Need for a new medication on relapse is urgent. The immunotherapy using Dendritic cells (DCs) combined with cytokine induced killer (CIK) cells holds promise for the adjuvant treatment of AL to eradicate or control residual disease. This randomized study was conducted to evaluate the feasibility and effective of genetically modified DCs combining to CIK immunotherapy in relapse AL after allo-HSCT.

In this prospective randomized study for patients with newly diagnosed acute promyelocytic leukemia, patients will be randomized (1:1) into two groups which receive retinoic acid and arsenic trioxide based treatment versus retinoic acid and chemotherapy based regimen.

The treatment of CML and the expected survival has been revolutionised since the introduction of tyrosine kinase inhibitors (TKIs) such as nilotinib. Despite their effectiveness, these drugs will never totally remove CML affected cells from the body. In order to achieve this goal, and potentially enable CML patients to live without the daily need for TKIs, other features of the patient's immune system may need to be harnessed. One possibility is using externally administered interferon (IFN) to augment the response induced by the TKI. This study will assess the response in terms of length of survival, detection of minimal disease levels and time until disease worsens in patients with chronic phase CML who are taking nilotinib and pegylated Interferon. Patients will commence taking nilotinib for 3 months, and once tolerated, will simultaneously be treated with injected pegIFN for up to 2 years. Patients can continue taking nilotinib beyond this time providing they are receiving benefit. Options are available for patients to decrease or increase their dose or to switch to another TKI, imatinib, to ensure a balance between drug effectiveness and minimal side effects is achieved.