Neoplasms

Blood and Lymph Conditions

All Conditions

Nervous System Diseases

Leukemia

Central Nervous System Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Phase I Starting Dose: Rituximab administered via lumbar puncture at dose of 10 - 25 mg twice weekly according to the dose escalation.

Phase II Rituximab Starting Dose: Maximum tolerated dose from Phase I.

Phase I: Starting dose Rituximab 10 mg intrathecally twice weekly until 2 consecutive CSF samples are negative for the presence of blast cells. Thereafter, rituximab 10 mg intrathecally weekly for additional 4 weeks, followed by intrathecal rituximab 10 mg administered once every other week for an additional 8 weeks.

Phase II Starting Dose of Rituximab: Maximum tolerated dose from Phase I.

Intrathecal Rituximab

Elias Jabbour, MD

The goal of this clinical research study is to learn about the safety and effectiveness of rituximab given by spinal tap in patients with lymphoid malignancies involving the central nervous system.

A spinal tap (also called a lumbar puncture) is when fluid surrounding the spinal cord is collected by inserting a needle into the lower back. The affected area is numbed with local anesthetic during the procedure. It will also be used to give chemotherapy in this study.

Rituximab is designed to bind to a protein, called CD20, that is on the surface of the leukemia cells. This may cause the leukemia cells to die.

Study Groups and Study Drug Administration:

If you are found to be eligible, you will be assigned to a study group based on when you join this study. Up to 12 participants will be enrolled in the Phase I portion of the study, and up to 13 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of rituximab you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of rituximab. Each new group will receive a higher dose of rituximab than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of rituximab is found.

If you are enrolled in the Phase II portion, you will receive rituximab at the highest dose that was tolerated in the Phase I portion.

Study Visits:

Once enrolled, you will return to the clinic and receive the study drug by spinal tap up to 2 times a week. You will receive treatment twice a week until 2 CSF samples in a row do not show any leukemia cells. After that, you will receive treatment 1 time a week for an additional 4 weeks, and then you will receive treatment once every other week for an additional 8 weeks. The number of doses you receive will depend on how many doses the study doctor thinks is needed.

At each study visit the following procedures will be performed:

* You will have a physical exam, including measurement of your weight, and vital signs. °Your vital signs will be measured every 15 minutes for 1 hour after each dose of rituximab.
* You will be asked how well you are able to perform the normal activities of daily living (performance status).
* You will be asked about any drugs you may be taking and any side effects you may experiencing.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* A sample of cerebral spinal fluid may be collected from the lumbar puncture to verify the absence or presence of blast cells.

Follow-Up:

About 30 days after your last dose of study drug you will be contacted by the study staff by telephone and asked about any drugs you may be taking and any side effects you may experiencing. This call should take about 10 minutes.

Long-term Follow-up:

Every 6 to 12 months you may be contacted by the study staff by telephone and asked about any drugs you may be taking and any side effects you may experiencing. This call should take about 10 minutes.

You may be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

Length of Treatment:

The number of treatments you receive will depend on how long it takes for there to be no leukemia cells in the CSF samples. Once this happens, you will have treatments for an additional 12 weeks. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

This is an investigational study. Rituximab is FDA approved and commercially available for the treatment of relapsed and/or refractory lymphoid malignancies involving the central nervous system. Receiving rituximab by spinal tap is considered investigational.

Up to 25 patients will take part in this study. All will be enrolled at MD Anderson.

Intrathecal Rituximab in Lymphoid Malignancies Involving Central Nervous System

Safety and Efficacy of Intrathecal Rituximab in Patients With Lymphoid Malignancies Involving the Central Nervous System

The percentage of participants whose cancer shrinks or disappears after treatment where participants are considered as responding to therapy if the Cerebrospinal fluid (CSF) is without evidence of blast cells after four lumbar punctures with rituximab.

MTD is dose level at which at least 1 of 3 participants experiences a dose-limiting toxicity (DLT). DLTdefined as clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and meeting the NCI common terminology criteria that are CTCAE Grade 3 or 4.

M.D. Anderson Cancer Center

Phase I Starting Dose: Rituximab administered via lumbar puncture at dose of 10 - 25 mg twice weekly according to the dose escalation.

Phase II Rituximab Starting Dose: Maximum tolerated dose from Phase I.

Intrathecal Rituximab: Phase I: Starting dose Rituximab 10 mg intrathecally twice weekly until 2 consecutive CSF samples are negative for the presence of blast cells. Thereafter, rituximab 10 mg intrathecally weekly for additional 4 weeks, followed by intrathecal rituximab 10 mg administered once every other week for an additional 8 weeks.

Phase II Starting Dose of Rituximab: Maximum tolerated dose from Phase I.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Elias Jabbour MD/Associate Professor

Response Rate

Multiple dose levels were designed with a starting dose of 10 mg per injection followed by 25 mg once safety was established in the first 3 patients treated at the first dose level. The study moved tot he next dose level. Due to lack of response and slow accrual, participants were never treated on the next dose level and the study was terminated

Maximum Tolerated Dose (MTD) of Rituximab

Overall Study

Immune System Diseases

Rare Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Patients with active CNS leukemia at the time of lymphodepletion

Patients who were referred to CAR T-cells with CNS disease, which was cleared by the time of lymphodepletion

CAR T cells targeting CD19 have been approved for patients with relapsed or refractory ALL, failing two or more prior protocols. Several institutional-based studies with other CAR T cells targeting CD19 have demonstrated outstanding response rates in patients with refractory disease, and the ability of CAR T cells to clear CNS leukemia. Nevertheless, these cases are sparse and have never been reported collectively.

Here, we aim to retrospectively assess toxicity and long term outcome of patients treated with CAR T cells for CNS relapse of ALL.

A Retrospective Study of Patients With Leukemia Relapse in the CNS Treated With CAR T Cells

CARs for CNS-Leukemia Relapse: A Retrospective International Study

Duration between CAR T-cell infusion and death or last follow-up, according to Kaplan-Meier analysis

Number of patients and average grade of cytokine-release syndrome and immune-effector cell associated neurotoxicity syndrome within 2 months after CAR treatment, according to ASCTC guidelines (Lee et al, BBMT 2019)

Duration between CAR T-cell infusion and leukemia relapse, according to Kaplan-Meier analysis

Duration between CAR T-cell infusion and CNS leukemia relapse, according to Kaplan-Meier analysis

Sheba Medical Center

Head, Pediatric Cancer Immunotherapy

Diseases and Abnormalities at or Before Birth

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Congenital Abnormalities

Influenza, Human

Hematologic Neoplasms

Neoplasm, Residual

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Chromosome Aberrations

Monosomy

Chromosome Disorders

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neoplastic Processes

Bone Marrow Diseases

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Aneuploidy

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Neurofibromatosis

Neurofibromatosis Type 1

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Anticonvulsants

Nootropic Agents

Fludarabine

Fludarabine phosphate

Melphalan

Levetiracetam

Busulfan

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.

Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.

Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.

Busulfan 82.1 mg\*hr/L IV on days -5 to -2 or days -8 to -5

200 mg/m2 intravenous given once on day-1

As seizures have occurred following high dose busulfan, all patients will be treated with Keppra beginning day -6 and continuing until day -1 per institutional guidelines.

Margaret MacMillan

This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies

MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies

Phase II, Open-Label, Prospective Study of T Cell Receptor Alpha/Beta Depletion (A/B TCD) Peripheral Blood Stem Cell (PBSC) Transplantation for Children and Adults With Hematological Malignancies

For the purposes of data and safety monitoring, this study is classified as high risk (investigator initiated under an IND). Therefore the following requirements will be fulfilled:

* The Masonic Cancer Center Data and Safety Monitoring Council (DSMC) will review the study's progress at least quarterly.
* The PI will comply with at least twice yearly monitoring of the project by the Masonic Cancer Center monitoring services.
* The PI will oversee the submission of all reportable adverse events per the definition of reportable in Section 11.5 to the Masonic Cancer Center's SAE Coordinator, the University of Minnesota IRB, and the FDA.

Monitor median rate of engraftment by 42 days.

Determine the rate of graft failure by day 100 (defined as lack of achievement of an ANC \>=500/mL with associated pancytopenia)

Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year

Number of participants experiencing progression free survival at one year follow up

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intrathecal Rituximab in Lymphoid Malignancies Involving Central Nervous System	NCT01596127	Leukemia Lymphoid Malign... Metastatic Mali...	Intrathecal Rit...	3 Years -	M.D. Anderson Cancer Center
A Retrospective Study of Patients With Leukemia Relapse in the CNS Treated With CAR T Cells	NCT04158011	Acute Lymphobla...		-	Sheba Medical Center
MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies	NCT05735717	Hematologic Mal... Acute Leukemia Remission Acute Myeloid L... Acute Lymphobla... AML TP53 Intrachromosoma... Cytogenetic Abn... CNS Leukemia Minimal Residua... Myelodysplasia Juvenile Myelom... Somatic Mutatio... PTPN11 Gene Mut... N-RAS Gene Ampl... Neurofibromatos... NF1 Mutation CBL Gene Mutati... Monosomy 7 Chromosome Abno... Fetal Hemoglobi...	Fludarabine Busulfan Melphalan Rituximab Levetiracetam	- 60 Years	Masonic Cancer Center, University of Minnesota

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