Neoplasms

Eye Diseases

All Conditions

Diseases and Abnormalities at or Before Birth

Rare Diseases

Retinoblastoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Retinal Neoplasms

Eye Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Single group assignment of patients with intraocular retinoblastoma, unilateral or bilateral.

Drug administered intra-arterially (injection in the artery).

Standard dose:

2.5mg (3-6 month old) 3.0 mg (6-12 month old) 4.0 mg (1-3 year old) 5.0 mg (\>3 years old)

Dose modification: decrease standard dose by 25% if there are signs of toxicity. Increase the dose by 25% if there is inadequate tumor response.

Frequency: 2 treatment cycles at 3-4 week intervals, with a third treatment cycle administered if the tumor requires it.

Dose not to exceed 0.5mg/kg, per treatment cycle.

Melphalan hydrochloride

Monica Pearl, M.D.

The purpose of this study is to show that chemotherapy delivered directly through the artery supplying the eye (ophthalmic artery) to patients with retinoblastoma is a safe and effective treatment alternative to conventional systemic chemotherapy, external beam radiation, and surgical removal of the eye.

Delivering the chemotherapeutic agent in the arterial system through the ophthalmic artery transforms the treatment of retinoblastoma from systemic chemotherapy to local chemotherapy. Administration of the drug directly to the targeted site thus avoids the complications and adverse events associated with toxicity from systemic, rather than local, chemotherapy.

Intra-arterial Chemotherapy for the Treatment of Intraocular Retinoblastoma

The primary objective of this study is to show that intra-arterial delivery of the chemotherapeutic agent is successful in treating intraocular retinoblastoma, defined as avoiding systemic chemotherapy, external beam radiation, and enucleation.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

IAC is offered to all patients with intraocular Rb who are deemed eligible after evaluation under anesthesia (EUA),with the exception of those few patients for whom focal modalities (i.e., laser or cryotherapy) would be effective.In cases of bilateral disease, both eyes would be treated sequentially during the same procedure utilizing the same femoral access site.

Two cycles of IAC will be performed at 3 to 4 week intervals. Melphalan dosing: 3-6 mth-old, 2.5mg; 3-12 mth-old, 3mg; 1-3 yr-old, 4mg; \>3 yr-old, 5mg. For those tumors that have shown appropriate response and are amenable to local therapies, then no additional IAC will be performed. If the tumors do not regress after 2 cycles, then a third cycle of IAC will be offered. Local therapies (laser, cryotherapy) will not be given during the EUAs conducted prior to each treatment session, but will be allowed after toxicity and response has been assessed 3-4 weeks after the final cycle of intra-arterial therapy.

Intra-arterial Chemotherapy

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Number of Patients Who Complete Therapy Without the Need for Additional Treatment Including Systemic Chemotherapy, External Beam Radiation, or Enucleation.

Overall Study

Nervous System Diseases

Glioma

Diffuse Intrinsic Pontine Glioma

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

IA melphalan is administered via the basilar artery.

Drug administered intra-arterially (injection in the artery).

Standard dose: Cycle 1: 1 mg, intra-arterial (IA) delivery. Cycle 2: 2 mg, intra-arterial (IA) delivery.

Duration of treatment: Eight weeks total - two cycles of IA chemotherapy, separated by four weeks.

The goal of this pilot study is to determine if intra-arterial (IA) chemotherapy is safe in the treatment of progressive diffuse intrinsic pontine gliomas (DIPG). IA administration of the chemotherapeutic agent enhances the regional distribution of the drug, thereby increasing the local delivered dose while minimizing systemic toxicity. It also provides a treatment option for these patients at the time of tumor recurrence.

Delivering the chemotherapeutic agent directly to the tumor via the arterial system avoids the complications and adverse events associated with toxicity from systemic chemotherapy.

Intra-arterial Chemotherapy for the Treatment of Progressive Diffuse Intrinsic Pontine Gliomas (DIPG).

Number of participants with grades 3-5 intracranial hemorrhage, grades 3-5 stroke, as defined by the Nervous system disorder CTCAE, and requirement of blood transfusion.

Number of months until disease progression.

Solving Kids' Cancer

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Heart and Blood Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Anemia

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Anemia, Aplastic

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Graft vs Host Disease

Hodgkin Disease

Myeloproliferative Disorders

Neoplasm, Residual

Waldenstrom Macroglobulinemia

Pathologic Complete Response

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Bone Marrow Failure Disorders

Pancytopenia

Myelodysplastic-Myeloproliferative Diseases

Neoplastic Processes

Disease Progression

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Aplastic Anemia

Chronic Myeloid Leukemia

Homologous Wasting Disease

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Antirheumatic Agents

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Mycophenolic Acid

Sirolimus

Temsirolimus

MTOR Inhibitors

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1.

STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Undergo allogeneic hematopoietic stem cell transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Fludarabine Phosphate

Laboratory Biomarker Analysis

Melphalan Hydrochloride

Mycophenolate Mofetil

Total-Body Irradiation

Maureen Ross

This phase Ib/2 trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer 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 (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.

PRIMARY OBJECTIVES:

I. To determine the cumulative incidence of extensive chronic graft versus host disease (GVHD) at 1 year after transplantation utilizing the novel conditioning/GVHD prophylactic regimen for patients undergoing allogeneic hematopoietic cell transplantation, in patients who do not progress before day 100.

SECONDARY OBJECTIVES:

I. To evaluate clinical response, engraftment rate, progression-free survival (PFS) at one year and, overall survival (OS).

II. To determine the cumulative incidence of relapse. III. To evaluate the day 100 transplant-related mortality rate. IV. To determine the cumulative incidence of grade III-IV acute GVHD.

OUTLINE: This is a dose-escalation study of melphalan hydrochloride.

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo total body irradiation (TBI) on day -1.

STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and tacrolimus IV and then orally (PO) once tolerated on days 5-180 with a taper beginning on day 100.

After completion of study treatment, patients are followed up for 12 months and then annually thereafter.

Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

A Phase Ib/2 Trial of Fludarabine/Melphalan/Total Body Irradiation With Post Transplant Cyclophosphamide as Graft Versus Host Disease Prophylaxis in Matched-Related and Matched-Unrelated Allogeneic Hematopoietic Cell Transplantation

Will be analyzed for each stratum. Will examine in a post-hoc analysis potential chronic GVHD rates of response by human leukocyte antigen (HLA) matching status.

Will utilize either straight Kaplan-Meier based estimators or extensions of nonparametric survival models to account for competing risks.

Will be analyzed in a descriptive fashion with means +/- standard deviations or frequency counts. Will examine in a post-hoc analysis potential chronic GVHD rates of response by human leukocyte antigen (HLA) matching status.

Will be analyzed in a descriptive fashion with means +/- standard deviations or frequency counts.

Roswell Park Cancer Institute

Recurrence

Patients receive personalized dose of melphalan hydrochloride IV on day -2 for for predicted 3-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.

Patients receive personalized dose of melphalan hydrochloride IV on day -2 for predicted 5-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.

Given personalized dose IV for predicted 3-day duration of severe neutropenia

Given personalized dose IV for predicted 5-day duration of severe neutropenia

Pharmacological Study

Ashley Rosko, MD

This randomized phase II trial studies the side effects and how well melphalan hydrochloride works in treating patients with multiple myeloma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

PRIMARY OBJECTIVES:

I. Identify whether targeting approximate (approx.) 3- or 5-days of severe neutropenia after exposure to a personalized melphalan hydrochloride (melphalan) dose results in best clinical outcome.

II. Measure melphalan-related toxicities in both 3-day and 5-day arms. III. Measure response per International Myeloma Working Group (IMWG). IV. Record overall survival (OS) and progression free survival (PFS).

SECONDARY OBJECTIVES:

I. To administer a test dose of melphalan and obtain test dose melphalan pharmacokinetics (PK) data from the first 33 patients.

II. Measure drug-induced deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs) treated with melphalan ex vivo post exposure.

III. Measure drug-induced DNA damage in patient myeloma cells treated with melphalan ex vivo.

IV. Assess melphalan-induced DNA damage in treated patients. V. Measure allele and genotype frequencies of variants, as well as gene expression of XRCC1 rs25487 and XRCC3 rs861529.

VI. Additional genetic variants relevant to DNA repair, melphalan transport, and clinical toxicities may be tested as well.

VII. Test cytotoxicity (half maximal inhibitory concentration \[IC50\]) of patient PBMCs prior to autologous transplant after exposure to melphalan ex vivo.

VIII. Measure p53 and phospho(TP53) in patient PBMCs prior to autologous transplant at baseline and after exposure to melphalan ex vivo.

IX. Incorporate both disease progression and drug-related toxicities into separate models linked to our calculated melphalan area under the curve (AUC) model.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients receive personalized dose of melphalan hydrochloride intravenously (IV) on day -2 for predicted 3-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.

ARM II: Patients receive personalized dose of melphalan hydrochloride IV on day -2 for predicted 5-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.

After completion of study treatment, patients are followed up for 30 days, at 3 months after transplant, and then every 6-12 months.

Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant

Randomized Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant

Will compare DNA damage repair efficiency in patients that have minimal response to induction and high dose melphalan hydrochloride (partial response or less) compared to those that are sequencing minimal residual disease negative.

Will create a multivariate linear regression model that includes each patient?s IC50, DNA repair gene single nucleotide polymorphism (SNP) presence or absence, and revised Multiple Myeloma International Staging System with progression free survival as the outcome.

Will compare the prediction accuracy of melphalan hydrochloride pharmacokinetics using the test dose versus the current PK model. Test the use of aspects of test dose PK as a covariate in the current high dose melphalan hydrochloride prediction model.

Will correlate with progression free survival.

Will determine the parameter accuracy and precision of the newly integrated PK/PD model for absolute neutrophil count, mucositis, tachyarrhythmias, and disease progression.

Will use Cox survival analysis, measure progression free survival of patients with XRCC1 rs25487 and XRCC3 rs861529 variant alleles compared to wild type.

Complete response will be defined as complete response + stringent complete response according to the International Myeloma Working Group Uniform response criterion. Will be calculated with an exact 95% confidence interval, both within arms and across arms.

Will assess melphalan-related toxicities (possibly, probably, or definitely related to high dose melphalan) including the incidence of grade 3/4 mucositis, grade 3/4 bacteremia, length of inpatient stay, duration of severe neutropenia (absolute neutrophil count \< 500), duration of severe thrombocytopenia (Platelet \< 20K), and proportion with tachyarrhythmias (e.g. atrial fibrillation with rapid ventricular rate).

Will be assessed by standard next generation sequencing.

National Cancer Institute (NCI)

Ohio State University Comprehensive Cancer Center

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intra-arterial Chemotherapy for the Treatment of Intraocular Retinoblastoma	NCT01293539	Retinoblastoma	Melphalan hydro...	- 18 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Intra-arterial Chemotherapy for the Treatment of Progressive Diffuse Intrinsic Pontine Gliomas (DIPG).	NCT01688401	Diffuse Intrins...	Melphalan hydro...	1 Month - 17 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Intra-arterial Chemotherapy for the Treatment of Progressive Diffuse Intrinsic Pontine Gliomas (DIPG).	NCT01688401	Diffuse Intrins...	Melphalan hydro...	1 Month - 17 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Intra-arterial Chemotherapy for the Treatment of Intraocular Retinoblastoma	NCT01293539	Retinoblastoma	Melphalan hydro...	- 18 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant	NCT03192397	Acute Myeloid L... Adult Acute Lym... Chronic Myeloge... Chronic Myelomo... Graft Versus Ho... Hodgkin Lymphom... Minimal Residua... Myelodysplastic... Myeloproliferat... Non-Hodgkin Lym... Plasma Cell Mye... Severe Aplastic... Waldenstrom Mac...	Allogeneic Hema... Cyclophosphamid... Fludarabine Pho... Laboratory Biom... Melphalan Hydro... Mycophenolate M... Sirolimus Total-Body Irra...	18 Years -	Roswell Park Cancer Institute
Intra-arterial Chemotherapy for the Treatment of Intraocular Retinoblastoma	NCT01293539	Retinoblastoma	Melphalan hydro...	- 18 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant	NCT03328936	Hematopoietic C... Recurrent Plasm... Refractory Plas...	Laboratory Biom... Melphalan Hydro... Melphalan Hydro... Pharmacological...	18 Years -	Ohio State University Comprehensive Cancer Center
Intra-arterial Chemotherapy for the Treatment of Progressive Diffuse Intrinsic Pontine Gliomas (DIPG).	NCT01688401	Diffuse Intrins...	Melphalan hydro...	1 Month - 17 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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