Neoplasms

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Diseases and Abnormalities at or Before Birth

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Heart and Blood Diseases

Rare Diseases

Neoplasm Metastasis

Syndrome

Recurrence

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Congenital Abnormalities

Anemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Polycythemia Vera

Polycythemia

Preleukemia

Myelodysplastic Syndromes

Wilms Tumor

Thrombocytosis

Thrombocythemia, Essential

Anemia, Refractory, with Excess of Blasts

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Anemia, Refractory

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Disease Attributes

Bone Marrow Diseases

Precancerous Conditions

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Chronic Disease

Myelodysplastic-Myeloproliferative Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Wilms' Tumor

Essential Thrombocythemia

Myelodysplastic Syndrome With Excess Blasts

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Lymphosarcoma

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Aldesleukin

Immunomodulating Agents

Interleukin-2

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

therapeutic allogeneic lymphocytes

aldesleukin

peripheral blood stem cell transplantation

allogeneic bone marrow transplantation

laboratory biomarker analysis

gene expression analysis

immunologic technique

flow cytometry

polymerase chain reaction

cytogenetic analysis

staining method

Merav Bar

This phase I/II trial is studying the side effects of biological therapy and to see how well it works in treating patients with advanced myelodysplastic syndrome, chronic myeloid leukemia, acute myeloid leukemia, or acute lymphoblastic leukemia. Biological therapies, including immunotherapy, can potentially be used to stimulate the immune system and stop cancer cells from growing. Immunotherapy given to patients who have undergone donor stem cell transplantation may be a way to eradicate remaining cancer cells

PRIMARY OBJECTIVES:

I. To determine the safety and potential toxicities associated with infusing donor CD8+ cytotoxic T lymphocyte (CTL) clones specific for Wilms' tumor (WT1) in patients who have relapsed or at a high risk of relapse post transplant for myelodysplastic syndromes (MDS), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL).

SECONDARY OBJECTIVES:

I. To determine the in vivo persistence of transferred T cells and assess migration to the bone marrow, a predominant site of leukemic relapse.

II. To determine if adoptively transferred WT1-specific T cells mediate antileukemic activity.

OUTLINE: Donors undergo leukapheresis for stem cell harvest to generate CD8-positive WT1 gene-specific CTL clones at the time of allogeneic stem cell transplantation.

After post-transplantation hematopoietic recovery, patients receive treatment for either highest-risk disease (prophylactically) or relapsed disease.

Highest-risk disease group: Patients receive CD8-positive WT1 gene-specific CTL clones intravenously (IV) over 1-2 hours on days 0, 14, and 28. Beginning 2-4 hours after CTL infusion, patients receive interleukin-2 subcutaneously (SC) twice daily on days 28-42 in the absence of unacceptable toxicity.

Relapsed-disease group: Some patients with evidence of leukemic relapse may receive standard salvage chemotherapy prior to donor CTL infusions and then receive CD8-positive WT1 gene-specific CTL clones and interleukin-2 as in the highest-risk group.

Patients in both groups who have progressive disease after complete or partial response to therapy may be eligible for retreatment with CD8-positive WT1 gene-specific CTL clones.

After completion of study treatment, patients are followed every 3 months for 2 years.

Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

Phase I/II Study of Adoptive Immunotherapy With CD8+ WT1-Specific CTL Clones for Patients With Advanced MDS, CML, AML or ALL After Allogeneic Hematopoietic Stem Cell Transplant

Assessed by Common Terminology Criteria (CTC) version 3.0.

Patients achieving complete remission with chemotherapy and T cell infusions will be followed to determine the duration of response. The proportion of responders will be estimated with associated confidence intervals. Duration of remission will be summarized using time-to-event methods, which will allow estimates to be made while some patients remain in remission.

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Principal Investigator

Skin and Connective Tissue Diseases

Melanoma

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

Neuroendocrine Tumor

Neuroepithelioma

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients with an established biorhythm receive TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.

temozolomide

biopsy

Roxana Dronca, M.D.

This clinical trial studies individualized temozolomide (TMZ) in treating patients with stage IV melanoma that cannot be removed by surgery. Drugs used in chemotherapy, such as TMZ, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving TMZ at different times, which are determined individually for each patient based on the phase (biorhythm) of the immune system response against the tumor may allow for a better drug response and may kill more tumor cells

PRIMARY OBJECTIVES: I. To assess the clinical activity of timed administration of TMZ therapy in patients with stage IV melanoma who have or have not received prior chemotherapy for metastatic melanoma. SECONDARY OBJECTIVES: I. To assess the toxicity profile of timed administration of TMZ therapy in patients with stage IV melanoma who have or have not received prior chemotherapy for their metastatic disease. II. To evaluate the parameters of immune homeostasis that are associated with the anti-tumor immune biorhythm in order to gain insight into the mechanism of the observed clinical and immunological effect of timed TMZ chemotherapy. III. To evaluate the impact of timed TMZ chemotherapy on immune biomarkers and the anti-tumor immune biorhythms. OUTLINE: Prior to initiation of therapy patients will undergo a period of immunologic monitoring to analyze the bioperiodicity of their anti-tumor immune response. Patients with an established biorhythm will receive TMZ orally (PO) starting on the recommended day for 5 days. Treatment repeats every 21-42 days (based on the established biorhythm) until of disease progression or unacceptable toxicity. Patients without an established biorhythm are given the option to go off study or receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 2 years.

Individualized Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

Individualized (Timed) Temozolomide Administration as a Means of Immune Reconstitution in Patients With Metastatic Melanoma

The distribution of time to progression will be estimated using the method of Kaplan-Meier and the 4 month progression-free rate (percentage) will be provided. Progression is defined as: At least one of the following must be true: At least one new malignant lesion, which also includes any lymph node that was normal at baseline (\< 1.0 cm short axis) and increased to ≥ 1.0 cm short axis during follow-up. At least a 20% increase in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the MSD. In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.

Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined as:At least one of the following must be true: At least one new malignant lesion, which also includes any lymph node that was normal at baseline (\< 1.0 cm short axis) and increased to ≥ 1.0 cm short axis during follow-up. At least a 20% increase in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the MSD (Section 11.41). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Mayo Clinic

The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).

Treatment (Individualized Chemotherapy)

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Roxana S. Dronca, M.D.

Patients with an established biorhythm receive timed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.

Treatment (Timed Individualized Chemotherapy)

Only patients who were evaluable for the primary endpoint were included in the analysis.

Progression-Free Survival at 4 Months

Patients with an established biorhythm receive untimed TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.

Treatment (Untimed Individualized Chemotherapy)

Progression-Free Survival

Overall Survival

Fatigue

Febrile Neutropenia

Neutrophil Count Decreased

Platelet Count Decreased

Sepsis

Urinary Tract Infection

White Blood Cell Decreased

Abdominal Infection

Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)

To Evaluate the Impact of Timed TMZ Chemotherapy on Immune Biomarkers and the Anti-tumor Immune Biorhythms.

To Evaluate the Parameters of Immune Homeostasis That Are Associated With the Anti-tumor Immune Biorhythm in Order to Gain Insight Into the Mechanism of the Observed Clinical and Immunological Effect of Timed TMZ Chemotherapy

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation	NCT00052520	Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... B-cell Adult Ac... B-cell Childhoo... Childhood Chron... Childhood Myelo... Chronic Myelomo... Essential Throm... Polycythemia Ve... Previously Trea... Recurrent Adult... Recurrent Adult... Recurrent Child... Recurrent Child... Refractory Anem... Refractory Anem... Relapsing Chron... Secondary Acute... T-cell Adult Ac... T-cell Childhoo...	therapeutic all... aldesleukin peripheral bloo... allogeneic bone... laboratory biom... gene expression... immunologic tec... flow cytometry polymerase chai... cytogenetic ana... staining method	-	Fred Hutchinson Cancer Center
Individualized Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery	NCT01328535	Recurrent Melan... Stage IV Melano...	temozolomide flow cytometry staining method biopsy laboratory biom...	18 Years -	Mayo Clinic
Individualized Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery	NCT01328535	Recurrent Melan... Stage IV Melano...	temozolomide flow cytometry staining method biopsy laboratory biom...	18 Years -	Mayo Clinic

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