Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Preleukemia

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Leukemia, Lymphoid

Anemia

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, B-Cell

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Neoplasms by Histologic Type

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Disease Attributes

Cell Transformation, Neoplastic

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Neoplastic Processes

Myeloid Leukemia

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Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Participants receive MK-0457 as a continuous intravenous infusion (CIV) at assigned dose and duration

MK0457

Medical Monitor

In this study participants with relapsed/refractory leukemia will be given MK-0457 in sequential cohorts and with varying treatment duration to determine the maximum tolerated dose (MTD) for MK-0457.

MK0457 in Patients With Leukemia (0457-003)

A Phase I/II Dose Escalation Study of MK0457 in Patients With Leukemia

Merck Sharp & Dohme LLC

Infections

Heart and Blood Diseases

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Hematologic Neoplasms

Leukemia, Myeloid, Acute

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Burkitt Lymphoma

Anemia, Refractory, with Excess of Blasts

Waldenstrom Macroglobulinemia

Lymphoma, Non-Hodgkin

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

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Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Includes dose adjustment of T regulatory (Treg) and CD3+ T effector (CD3+ Teff) cells in recipients of double UCB transplantation

Given by infusion on Day 0 after transplantation - Five doses of Treg (3 x 10\^6/kg, 10 x 10\^6/kg, 30 x 10\^6/kg, 100 x 10\^6/kg and 300 x 10\^6/kg)

Treg cells

Given by infusion on Day 0 after transplantation - 5 doses of CD3+ Teff cells (3 x 10\^6 cells/kg, 6 x 10\^6 cells/kg, 9 x 10\^6 cells/kg, 12 x 10\^6 cells/kg, and 15 x 10\^6 cells/kg with the latter dose representing the median number of CD3+ cells in two UCB unit grafts

CD3+ Teff cells

Given intravenously on Days -8 through -6, 25 mg/m\^2 over 1 hour

Given intravenously on Day -7 and -6, 60 mg/kg

Given on Days -4 through -2, 165 cGY twice a day.

Total body irradiation

Umbilical cord blood transplantation

Claudio Brunstein, MD, PhD

This is a unique dose-escalation trial that will titrate doses of umbilical cord blood (UCB) Treg and CD3+ Teff cells with the goal of infusing as many CD3+ Teff cells as possible without conferring grade II-IV acute graft-versus-host disease (GVHD).

In this study, the investigators propose to add UCB Treg and UCB CD3+ Teff cells to the two TCD UCB donor units with the goal of transplanting as many CD3+ Teff cells as possible without reintroducing risk of acute GVHD. The investigators hypothesize that Treg will permit the reintroduction of CD3+ Teff cells that will provide a bridge while awaiting HSC T cell recovery long term. The co-infusion of Treg will prevent GVHD without the need for prolonged pharmacologic immunosuppression.

Based on prior studies, the first patient will start at lowest dose combination (3 x 10\^6/kg of Treg and 3 x 10\^6/kg of CD3+ Teff cells).

One patient will be entered at each level with a minimum of 35 days to observe the patient prior to moving to the next dose level. (1) If GVHD does not occur, a "successful step", then the CD3+ Teff cell dose will increase to the next higher level for the next patient; (2) If GVHD occurs, a "failed step", then Treg dose will increase to the next higher level for the next patient. It would take a minimum of 5 (if no GVHD) and maximum of 9 patients (if GVHD is observed at each level) to complete all Treg:CD3+ Teff cell combinations.

An additional 10 patients will be enrolled to verify that this reflects the optimal combination and evaluate its safety profile.

T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies

Optimization of the T Regulatory Cell and T Effector Cell Doses in Recipients of Double UCB Transplantation for Treatment of Hematological Malignancies

Determine the optimal cell dose mixture of UCB T regulatory and CD3+ T effector cells without the development of grade II-IV acute GVHD

reaction that occurs with 48 hours of product infusion

Determine the incidence of neutrophil recovery (absolute neutrophil count ≥ 500/uL) at day 42

Determine incidence of double and single unit chimerism at various time points

Determine incidence of viral and fungal infections at 1 year

Estimate the probability of survival at 1 year

Determine the incidence of grade III-IV acute GVHD at day 100

Determine the incidence of treatment related mortality (TRM) at 6 months

Determine the incidence of platelet recovery (platelet count ≥ 50,000/uL) at 1 year

Determine the incidence of chronic GVHD at 1 year

Determine the incidence of relapse at 1 year

Masonic Cancer Center, University of Minnesota

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MK0457 in Patients With Leukemia (0457-003)	NCT00111683	Chronic Myeloge... Lymphocytic Leu... Myelodysplastic... Myelogenous Leu...	MK0457	18 Years -	Merck Sharp & Dohme LLC
T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies	NCT01163201	Hematologic Mal... Acute Myeloid L... Acute Lymphocyt... Chronic Myeloge... Anemia, Refract... Chronic Myelopr... Chronic Lymphoc... Small Lymphocyt... Marginal Zone B... Follicular Lymp... Lymphoplasmacyt... Mantle-Cell Lym... Prolymphocytic ... Large Cell Non-... Lymphoblastic L... Burkitt's Lymph... High Grade Non-...	Treg cells CD3+ Teff cells Fludarabine Cyclophosphamid... Total body irra... Umbilical cord ...	18 Years - 55 Years	Masonic Cancer Center, University of Minnesota
T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies	NCT01163201	Hematologic Mal... Acute Myeloid L... Acute Lymphocyt... Chronic Myeloge... Anemia, Refract... Chronic Myelopr... Chronic Lymphoc... Small Lymphocyt... Marginal Zone B... Follicular Lymp... Lymphoplasmacyt... Mantle-Cell Lym... Prolymphocytic ... Large Cell Non-... Lymphoblastic L... Burkitt's Lymph... High Grade Non-...	Treg cells CD3+ Teff cells Fludarabine Cyclophosphamid... Total body irra... Umbilical cord ...	18 Years - 55 Years	Masonic Cancer Center, University of Minnesota
MK0457 in Patients With Leukemia (0457-003)	NCT00111683	Chronic Myeloge... Lymphocytic Leu... Myelodysplastic... Myelogenous Leu...	MK0457	18 Years -	Merck Sharp & Dohme LLC

Spots Global Cancer Trial Database for chronic myelogenous leukemia in blast crisis