Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Preleukemia

Myelodysplastic Syndromes

Leukemia, Lymphoid

Anemia

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, B-Cell

Anemia, Refractory

Blast Crisis

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

Myeloid Leukemia

Chronic Graft Versus Host Disease

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

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Interferons

Interferon-alpha

Peginterferon alfa-2a

Interferon alpha-2

Antiviral Agents

Participants will receive peginterferon alfa-2a subcutaneously in doses between 90 and 450 microgram (mcg) once weekly until medically indicated as judged by the treating investigator.

Peginterferon alfa-2a in doses between 90 and 450 mcg will be administered subcutaneously once weekly until medically indicated as judged by the treating investigator.

Clinical Trials

This study will evaluate the efficacy, safety and tolerability of long-term use of peginterferon alfa-2a in participants with CML who have previously participated in peginterferon alfa-2a study ML16544 (NCT number not available), NO16006 (NCT number not available) or ML17228 (NCT number not available) and treating physician has decided to continue treatment with peginterferon alfa-2a within the frame of another clinical study.

Expanded Access Study With Peginterferon Alfa-2a (Pegasys) in Participants With Chronic Myelogenous Leukemia (CML)

Multicenter Open Label Expanded Access-Program of Pegylated Interferon Alfa-2a (Pegasys) in Patients With Chronic Myelogenous Leukemia (CML)

Hematologic response was considered to be achieved if participants met all of the following criteria: normalization of white blood cells count to less than (\<) 10\*10\^9 per liter (/L) with normal differentiation, normalization of platelet count at \<450\*10\^9/L, and disappearance of all signs and symptoms of the disease. This response had to be confirmed at least 4 weeks after the first measure and beyond that.

Time to loss of previous hematologic response was defined as the interval between the first day of treatment in the study and the first day of loss of previous hematologic response during elapsed time of study. Hematologic response was considered to be achieved if participants met all of the following criteria: normalization of white blood cells count to \<10\*10\^9/L with normal differentiation, normalization of platelet count at \<450\*10\^9/L, and disappearance of all signs and symptoms of the disease. This response had to be confirmed at least 4 weeks after the first measure and beyond that.

CyR was based on the prevalence of Philadelphia chromosome-positive (Ph+) bone marrow cells in metaphase determined from reverse transcriptase polymerase chain reaction (RT-PCR). Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was absence of detectable Ph+ bone marrow cells and PCyR was achieved when 1 to 34 percent (%) of bone marrow cells were Ph+.

Time to loss of previous CyR was defined as the interval between the first day of treatment in the study and the first day of loss of previous CyR. CyR is based on the prevalence of Ph+ bone marrow cells in metaphase. Major CyR was categorized as either CCyR or PCyR. CCyR was achieved when there was absence of detectable Ph+ bone marrow cells and PCyR was achieved when 1 to 34% of bone marrow cells were Ph+.

MR was assessed using breakpoint cluster region - Abelson (BCR-ABL) proto-oncogene transcript levels measured by RT-PCR from peripheral blood. Number of participants with BCR-ABL/ABL ratio less than or equal to 10 (%) was reported.

Time to loss of previous MR was defined as the interval between the first day of treatment in the study and the first day of loss of previous MR. MR was assessed using BCR-ABL transcript levels measured by RT-PCR from peripheral blood.

Hoffmann-La Roche

Analysis population included all enrolled participants.

Participants who have previously participated in study ML16544, NO16006, or ML17228 and deemed to be a responder, received peginterferon alfa-2a subcutaneously in doses between 90 and 450 mcg once weekly until medically indicated as judged by the treating investigator. Maximum treatment duration was approximately up to 7 years.

Peginterferon Alfa-2a

Age, Continuous

Sex: Female, Male

Medical Communications

Number of Participants With Complete Hematologic Response

Time to Loss of Previous Hematologic Response

Number of Participants With Major Cytogenetic Response (CyR)

Time to Loss of Previous CyR

Number of Participants With Molecular Response (MR)

Time to Loss of Previous MR

Participants who have previously participated in study ML16544 (NCT number not available), NO16006 (NCT number not available) or ML17228 (NCT number not available) and deemed to be a responder, received peginterferon alfa-2a subcutaneously in doses between 90 and 450 microgram (mcg) once weekly until medically indicated as judged by the treating investigator. Maximum treatment duration was approximately up to 7 years.

Overall Study

Skin and Connective Tissue Diseases

Recurrence

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Hematologic Neoplasms

Melanoma

Leukemia, Myeloid, Acute

Lymphoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Lymphosarcoma

Neuroendocrine Tumor

Neuroepithelioma

Busulfan

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Immunoablative conditioning chemotherapy regimen, followed by transplantation of peripheral blood stem cells on Day 0 of the conditioning regimen.

Immunoablative Hematopoietic PBSC Transplant

Pharmacokinetics of once-a-day dosing of intravenous busulfan as a 3-hour infusion

Busulfan pharmacokinetics

* Patients diagnosed with ALL over 1 year of age and without prior CNS disease will receive CNS prophylaxis radiation to the whole brain prior to transplant.
* Patients diagnosed with ALL with prior CNS disease over the age of 1 year will be treated with prophylaxis radiation to the whole brain and spine prior to transplant.

Central Nervous System (CNS) prophylaxis radiation

Morris Kletzel, M.D.

The purpose of this research study is to evaluate the effectiveness of transplantation of high doses of peripheral blood stem cells (stem cells are special cells found in the blood and bone marrow that produce new blood cells) after treatment with non-myeloablative chemotherapy (not toxic to the bone marrow). In addition, this study will assess the side effects of the transplant.

The standard treatment in many disorders of the bone marrow is high dose chemotherapy and whole-body radiation treatment followed by the stem cell transplant. This type of transplant not only suppresses or kills off the immune system, but is very toxic to the bone marrow. This study uses a chemotherapy regimen that will suppress the patient's immune system; however, it is non-myeloablative (not toxic to the bone marrow). It does not use whole-body radiation treatment. This approach can minimize the short- and long-term effects of transplantation. Other studies have shown that using chemotherapy followed by bone marrow transplantation without whole-body radiation can produce similar results as treatment with whole-body radiation.

Patients will be given chemotherapy with Fludarabine and Busulfan prior to the stem cell transplant. This treatment not only destroys diseased cells, but it also kills normal bone marrow cells. Following this experimental treatment, the patient will be given the stem cells through a central venous catheter (tube inserted in a vein). When the healthy stem cells are given to the patient, they will replace the destroyed bone marrow cells and produce new blood cells. The Allogeneic (not one's own) stem cells used in this experimental transplant will be obtained from a related matched donor or from an unrelated matched donor located through the National Marrow Donor Program.

Immunoablative Mini Transplant (Hematopoietic Peripheral Blood Stem Cell Transplant [HPBSC])

Immunoablative Protocol for Allogeneic Related and Unrelated Hematopoietic Peripheral Blood Stem Cell Transplant (HPBSC)

Ann & Robert H Lurie Children's Hospital of Chicago

Philadelphia Chromosome

Lonafarnib

Enzyme Inhibitors

SCH66336

Jorge Cortes, MD

The goal of this research is to see if giving the drug SCH66336 by mouth can improve the disease in patients with chronic or accelerated phase CML. The safety of this treatment will also be studied.

Objectives for this study are two-fold:

1. To determine the efficacy of SCH66336 in patients with chronic phase and accelerated phase CML in relation to response rate, duration of response, and survival.
2. To assess the toxicity of SCH66366 in these patients.

Phase II Study of SCH66336, A Farnesyltransferase Inhibitor in Chronic Myelogenous Leukemia (CML)

M.D. Anderson Cancer Center

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Autologous HSP-70 Protein-Peptide Complex (AG-858) Plus Gleevec™.

This is a Phase II, exploratory, open-label study of the investigational product AG-858, in patients who are cytogenetically positive after treatment with Gleevec.

The trial will consist of three independent Phase II evaluations of patient groups according to their cytogenetic status as defined in the eligibility criteria (Eligibility Criteria 4a, 4b, and 4c).

The goals of this study are to determine the following:

* To estimate the proportion of patients with a complete cytogenetic response (CCR) within each patient group
* To estimate the proportion of patients with a substantial molecular response (SMR) within each patient group
* To evaluate the frequency and severity of adverse events.
* To assess the feasibility of AG-858 production.

AG-858 in Patients Who Are Cytogenetically Positive After Treatment With Gleevec™

Phase II Exploratory Study Of AG-858 Plus Gleevec™ In Patients With Chronic Myelogenous Leukemia (CML) In Chronic Phase Who Are Cytogenetically Positive After Treatment With Gleevec™

Agenus Inc.

Anemia, Aplastic

Hodgkin Disease

Primary Myelofibrosis

Leukemia, Lymphocytic, Chronic, B-Cell

Bone Marrow Failure Disorders

Pancytopenia

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

Bone Density Conservation Agents

Hormones

Teriparatide

Parathyroid Hormone

Hormone Antagonists

Calcium

Calcium, Dietary

Parathyroid hormone after double umbilical cord blood transplant.

Day +1: PTH 40 mcg, Day +2: PTH 60 mcg, Day +3: PTH 80 mcg, Day +4 to Day +29 or until ANC\>2000/microL: PTH 100 mcg

Parathyroid Hormone (teriparatide)

Karen K. Ballen, MD

Joseph Antin, MD

David Avigan, MD

Elizabeth J Shpall, MD

Colleen Delaney, MD

Ram Kamble, MD

Katarzyna Jamieson, M.D.

Philip McCarthy, M.D.

Edward Ball, M.D.

Richard Maziarz, M.D.

The purpose of this study is to determine whether the addition of parathyroid hormone after a sequential cord blood transplant will improve engraftment, which is the ability of the transplanted stem cells to grow and to successfully begin producing new blood cells.

In this phase II, single stage study, participants will include 40 adults who are candidates for a hematopoietic stem cell transplant. All participants will undergo a sequential cord blood transplant using a well-known myeloablative regimen of fludarabine, cyclophosphamide, and total body irradiation, which is appropriate for those individuals who are likely to benefit from an ablative regimen. Tacrolimus will be combined with mycophenolate mofetil (MMF) for the graft-versus-host disease (GVHD) prophylaxis regimen. Parathyroid hormone (PTH) will be added to this regimen in an attempt to improve engraftment. PTH is an approved drug with minimal side effects in individuals with osteoporosis; the dose of PTH has been determined from a phase I study in individuals with hematologic cancer.

Study of Parathyroid Hormone Following Sequential Cord Blood Transplantation From an Unrelated Donor

A Phase II Study of Parathyroid Hormone Following Myeloablative Sequential Unrelated Cord Blood Transplantation

Median time to neutrophil engraftment (defined as an absolute neutrophil count \[ANC\] greater than 500)

Cumulative Incidence of Acute GVHD Grades II-IV at day 100

Platelet engraftment (greater than 20,000)

National Heart, Lung, and Blood Institute (NHLBI)

The Emmes Company, LLC

Parathyroid Hormone (Teriparatide)

Age, Categorical

Age Continuous

Race (NIH/OMB)

United States

Region of Enrollment

The study was closed prematurely due to early mortality and lack of efficacy.

Adam Mendizabal, Statistician

Median Time to Neutrophil Engraftment (Defined as an Absolute Neutrophil Count [ANC] Greater Than 500)

Cumulative Incidence of Acute GVHD Grades II-IV at Day 100

Cumulative Incidence of Chronic GVHD

Platelet Engraftment (Greater Than 20,000)

100-day Transplant-related Mortality

Cumulative Incidence of Relapse

Overall Survival

Disease-free Survival

Leukocyte Disorders

Translocation, Genetic

Chromosome Aberrations

Nilotinib

Nilotinib was supplied as 50 mg, 150 mg and 200 mg hard gelatin capsules and administered orally at 300 mg BID (twice a day) or 400 mg BID (twice a day)depending on the randomized dose.

nilotinib

Imatinib was supplied as 100 mg and 400 mg tablets and administered orally at 400 mg QD (once a day).

imatinib

Novartis Pharmaceuticals

In this study, the efficacy and safety of two nilotinib doses, 300 mg twice daily and 400 mg twice daily, were compared with imatinib 400 mg once daily in newly diagnosed patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).

An extension protocol was included in this study design to allow patients who did not show sufficient response to their assigned treatments the opportunity to receive imatinib 400 mg BID (option available until protocol amendment 7) or nilotinib 400 mg BID, using an abbreviated safety and efficacy assessment schedule.

Primary objectives of this study:

* Compared the efficacy (major molecular response (MMR) rate at 12 months) of nilotinib at 400 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.
* Compared the efficacy (MMR rate at 12 months) of nilotinib at 300 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.

The Primary objectives of Extension Phase of the study:

- Characterized the safety and tolerability profile of nilotinib 400 mg BID after failure of imatinib or insufficiently responded to nilotinib 300 mg BID therapy and the safety and tolerability profile of imatinib therapy after failure of nilotinib therapy.

The study was designed to determine whether the treatment of newly diagnosed, previously untreated Ph+ CML-CP patients with either nilotinib 300 mg bid or 400 mg bid demonstrated improved efficacy compared to imatinib 400 mg qd. The primary efficacy endpoint was the rate of MMR defined as the proportion of patients who achieved ≥ 3 log reduction in BCR-ABL transcripts compared to either the standardized Baseline established in the IRIS trial (International Randomized Interferon versus STI571) (Cortes et al 2005) or to the BCR-ABL ratio ≤ 0.1% by International Scale, as detected by real-time quantitative polymerase chain reaction (RQ-PCR) at 12 months.

The key secondary endpoint was to compare the rate of durable MMR between nilotinib 300 mg bid with that of imatinib, and of nilotinib 400 mg bid with that of imatinib at 24 months. This report presents the final results of efficacy and safety at the LPLV (21-Aug-2019).

The main data analysis was done at the time when all patients completed 12 cycles of treatment (or discontinued earlier). There were two primary comparisons at this time point: the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg, and the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg. Comparisons were done sequentially, i.e. the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg was to be compared first; if it was significant at 5% level, the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg was to be compared. The study had a 90% power to detect a 15% difference between the nilotinib 400 mg arm versus imatinib 400 mg arm assuming that the MMR rate of imatinib is 40% and the MMR rate of nilotinib is 55%. The study also had a 90% power to detect a 15% difference between the nilotinib 300 mg and the imatinib 400 mg arms, if the comparison between the nilotinib 400 mg and the imatinib 400 mg was significant.

The second main data analysis was done at the time when all patients completed 24 cycles of treatment (or discontinued earlier). There were two key comparisons at this time point: the rate of durable MMR at 24 months of the nilotinib 400 mg versus the imatinib 400 mg, and the rate of durable MMR at 24 months of the nilotinib 300 mg versus the imatinib 400 mg.

In order to control the overall type I error rate at or below 5%, only when the corresponding comparison on the primary efficacy endpoint(s) was (were) significant, the key secondary comparison(s) of the respective nilotinib doses (400 mg bid and/or 300 mg bid) versus imatinib 400 mg qd were tested at two-sided 5% significance level.

Patients participating after demonstrating suboptimal response/treatment failure to their assigned study treatment in the core study were offered the option to continue in the extension study and to receive imatinib 400 mg bid (option available only until protocol amendment 7) or nilotinib therapy at a dose of 400 mg bid.

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
Expanded Access Study With Peginterferon Alfa-2a (Pegasys) in Participants With Chronic Myelogenous Leukemia (CML)	NCT02736721	Myelogenous Leu...	Peginterferon a...	18 Years -	Hoffmann-La Roche
Immunoablative Mini Transplant (Hematopoietic Peripheral Blood Stem Cell Transplant [HPBSC])	NCT00179764	Tumors Malignant Melan... Hematological M... Myelogenous Leu... Leukemia, Lymph...	Immunoablative ... Busulfan pharma... Central Nervous...	- 21 Years	Ann & Robert H Lurie Children's Hospital of Chicago
Phase II Study of SCH66336, A Farnesyltransferase Inhibitor in Chronic Myelogenous Leukemia (CML)	NCT00038597	Myelogenous Leu...	SCH66336	16 Years -	M.D. Anderson Cancer Center
AG-858 in Patients Who Are Cytogenetically Positive After Treatment With Gleevec™	NCT00058747	Leukemia, Myelo...	Autologous HSP-...	18 Years -	Agenus Inc.
MK0457 in Patients With Leukemia (0457-003)	NCT00111683	Chronic Myeloge... Lymphocytic Leu... Myelodysplastic... Myelogenous Leu...	MK0457	18 Years -	Merck Sharp & Dohme LLC
Study of Parathyroid Hormone Following Sequential Cord Blood Transplantation From an Unrelated Donor	NCT00393380	Leukemia, Myelo... Anemia, Aplasti... Myelofibrosis Lymphoma Hodgkin Disease Leukemia, Lymph... Leukemia, Myelo... Leukemia, Lymph...	Parathyroid Hor...	18 Years - 45 Years	The Emmes Company, LLC
A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)	NCT00471497	Myelogenous Leu...	nilotinib imatinib	18 Years -	Novartis

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