Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

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

Antineoplastic Agents

All Drugs and Chemicals

Blinatumomab

Blinatumomab+Haplo-Mismatched Cell Therapy (HMCT)

Blinatumomab per package insert - via continuous infusion days 1-28 of Cycle 1 and Cycle 2, every 42 days.

HMCT infusion Cycle 1, Day 15 and Cycle 2, Day 8 \& Day 15

Haplo-Mismatched Cell Therapy (HMCT)

Noah Merin, MD PhD

Single center Phase 1 dose escalation trial of the combination of standard-of-care blinatumomab plus Haplo-Mismatched Cellular Therapy (HMCT). HMCT refers to the infusion of donor peripheral blood mononuclear cells collected via pheresis from a haploidentical family member - the procedure is analogous to giving a donor lymphocyte infusion outside of the setting of an allogeneic stem cell transplant; also known as 'microtransplantation'. The HMCT is an unselected mix of lymphocytes and leukocytes, but the product dose escalation will be done based on the T cell content.

Ten recipients are planned. Each subject will be administered one infusion of HMCT during the first cycle of blinatumomab and two infusions during cycle two of blinatumomab; the CD3+ cell dose of the HMCT infusion is governed by dose escalation / de-escalation following a Bayesian method.

This single center, phase 1 study will examine the safety, side effects, and effectiveness of combining the investigational use of Haplo-Mismatched Cellular Therapy (HMCT) in combination with blinatumomab. Investigators plan to give HMCT starting on day 15, after the initial CRS caused by blinatumomab has resolved. The investigational treatment will start with 1% of the typical HMCT dose (10e6 CD3+ cells/kg) and will employ a modified dose escalation design as an additional safety measure. The primary end points will be DLT of the combination of blinatumomab and HMCT.

Blinatumomab Plus HLA-Mismatched Cellular Therapy for Relapsed/Refractory CD19+ ALL

IIT2017-05-MERIN-BLINHMCT: Blinatumomab Plus HLA-Mismatched Cellular Therapy (HMCT) for Relapsed/Refractory CD19+ ALL

Number of Dose Limiting Toxicities experienced by patients undergoing HLA mismatched cellular therapy (HMCT) of allogenic CD3+ cells in combination with blinatumomab.

Bone marrow aspiration and local peripheral blood counts will be used to measure response. CR is defined as the following:

* Less than or equal to 5% blasts in the bone marrow
* No evidence of disease, AND
* Full recovery of peripheral blood counts: platelets \> 100,000/ul, and ANC \> 1000/ul

Bone marrow aspiration and local peripheral blood counts will be used to measure response. CRh is defined as the following:

* Less than or equal to 5% blasts in the bone marrow
* No evidence of disease, AND
* Full recovery of peripheral blood counts: platelets \> 50,000/ul, and ANC \> 500/ul

Bone marrow aspiration and local peripheral blood counts will be used to measure response. CRi is defined as the following:

* Less than or equal to 5% blasts in the bone marrow
* No evidence of disease, AND
* Full recovery of peripheral blood counts: platelets \> 100,000/ul, and ANC \> 1000/ul

Bone marrow aspiration and local peripheral blood counts will be used to measure response. Blast-free hypoplastic or aplastic bone marrow response is defined as the following:

* Less than or equal to 5% blasts in the bone marrow
* No evidence of disease, AND
* Full recovery of peripheral blood counts: platelets \> 50,000/ul, and ANC \> 500/ul

MRD remission is defined as the occurrence of an MRD level below 10\^-4 measured by quantitative reverse transcription polymerase chain reaction (PCR) or flow cytometry.

Complete response defined as: no detectable leukemic cells by PCR or flow cytometry.

Amgen

Cedars-Sinai Medical Center

Assistant Clinical Professor, Principal Investigator

Symptoms and General Pathology

Syndrome

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Hematologic Neoplasms

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Anti-Inflammatory Agents

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Cytarabine

Methotrexate

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Folinic Acid

Folate

Vitamin B9

Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.

Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses).

Interventions:

* Cycle 1: cytarabine, HPC-A donor infusion
* Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion

Given by either intrathecal (IT) or intravenous (IV) route.

Intrathecal Triples

HPC-A

Jeffrey E. Rubnitz, MD, PhD

Allogeneic transplant can sometimes be an effective treatment for leukemia. In a traditional allogeneic transplant, patients receive very high doses of chemotherapy and/or radiation therapy, followed by an infusion of their donor's bone marrow or blood stem cells. The high-dose chemotherapy drugs and radiation are given to remove the leukemia cells in the body. The infusion of the donor's bone marrow or blood stem cells is given to replace the diseased bone marrow destroyed by the chemotherapy and/or radiation therapy. However, there are risks associated with allogeneic transplant. Many people have life-threatening or even fatal complications, like severe infections and a condition called graft-versus-host disease, which is caused when cells from the donor attack the normal tissue of the transplant patient.

Recently, several hospitals around the world have been using a different type of allogeneic transplant called a microtransplant. In this type of transplant, the donor is usually a family member who is not an exact match. In a microtransplant, leukemia patients get lower doses of chemotherapy than are used in traditional allogeneic transplants. The chemotherapy is followed by an infusion of their donor's peripheral blood stem cells. The objective of the microtransplant is to suppress the bone marrow by giving just enough chemotherapy to allow the donor cells to temporarily engraft (implant), but only at very low levels. The hope is that the donor cells will cause the body to mount an immunologic attack against the leukemia, generating a response called the "graft-versus-leukemia" effect or "graft-versus-cancer" effect, without causing the potentially serious complication of graft-versus-host disease.

With this research study, the investigators hope to find out whether or not microtransplantation will be a safe and effective treatment for children, adolescents and young adults with relapsed or refractory hematologic malignancies

PRIMARY OBJECTIVES:

* To assess the safety and feasibility of standard chemotherapy plus GCSF-mobilized Hematopoietic Progenitor Cell, Apheresis (HPC-A) in pediatric patients with relapsed or refractory hematologic malignancies.
* To estimate the response rates to standard chemotherapy plus GCSF-mobilized HPC-A in pediatric patients with relapsed or refractory hematologic malignancies.

SECONDARY OBJECTIVES:

* To describe the event-free and overall survival of patients treated with standard chemotherapy plus GCSF-mobilized HPC-A.
* To estimate the time to neutrophil and platelet recovery after treatment with standard chemotherapy plus GCSF-mobilized HPC-A.
* To determine the cumulative incidence of acute and chronic graft-versus-host disease (GVHD).

OTHER PRESPECIFIED OBJECTIVES:

* To characterize donor chimerism and microchimerism.

Patients will receive standard chemotherapy followed by infusion of donor peripheral blood mononuclear cells 2 days after the completion of chemotherapy. Patients who have at least a partial response are eligible to receive a second cycle.

Diagnostic lumbar puncture and intrathecal (IT) chemotherapy will be given prior to cycle 1. Patients without evidence of central nervous system (CNS) leukemia will receive no further IT therapy during cycle 1. Patients with CNS disease will receive weekly IT therapy (age-adjusted methotrexate, hydrocortisone, and cytarabine) until the cerebrospinal fluid (CSF) becomes free of leukemia (minimum of 4 doses).

Bone marrow aspiration (BMA) and biopsy to assess response will be performed on approximately day 29 of therapy.

For hematopoietic stem cell mobilization, donors will receive G-CSF (Filgrastim) (Neupogen®) each day for 5 days given subcutaneously (SQ) prior to HPC-A collected by leukapheresis on day 6.

Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

A Phase II Study of Microtransplantation in Patients With Refractory or Relapsed Hematologic Malignancies

Percent donor chimerism in blood and bone marrow.

If two or more patients die from causes other than leukemia progression or experience ≥ Grade 3 GVHD that is associated with detectable donor chimerism due to this protocol, or demonstrate persistent engraftment defined as \>5% donor chimerism at the time of count recovery (ANC \> 0.3 x 10\^9/L and platelet count \> 30 x 10\^/L), then the cohort will close due to intolerability. Any subject who transfers to transplant prior to completion of two courses without experiencing an unacceptable toxicity is considered inevaluable for purposes of evaluating tolerability. Accrual will be halted for intolerability if there are two or more failures in tolerability among the first six subjects who are evaluable for tolerability.

All patients will be counted towards this two-stage design. Therapeutic success for patients at time of enrollment is defined as:

* Patients with fewer than 5% blasts, a ≥ 10-fold decrease in level of minimal residual disease after completion of 1 or 2 cycles of therapy.
* Patients with greater than 5% in leukemic blasts in the marrow, achieving CR or CRi after completion of 1 or 2 cycles of therapy.

In terms of efficacy, patients who die before achieving therapeutic success will be counted as a failure, and all patients who receive ≥ 1 dose of protocol chemotherapy will be counted as a failure or success. Only subjects who withdraw or die prior to receiving the first dose of protocol chemotherapy will be considered inevaluable and replaced. The evaluation of tolerability and this phase II design will be performed concurrently, i.e., the first enrollees will be counted for both tolerability and efficacy.

We will use the Kaplan-Meier method to describe event-free survival. EFS will be defined as the time from enrollment to death, relapse, or refractory disease with event-free subjects' time censored at the date of last follow-up.

We will use the Kaplan-Meier method to describe overall survival. Overall survival will be defined as the time from enrollment to death, with living subjects' time censored at the date of last follow-up

The time to neutrophil recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of neutrophils, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events.

The time to platelet recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of platelets, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events.

Due to the small number of patients enrolled, the data is presented by patient.

Children's Oncology Group (COG) Stem Cell Committee Consensus Guidelines for Establishing Organ Stage and Overall Grade of Acute Graft Versus Host Disease (GVHD) were used. Overall clinical grade was based on the highest stage obtained:

* Grade 0: no stage 1-4 of any organ
* Grade I: stage 1-2 skin and no liver or gut involvement
* Grade II: stage 3 skin, or stage 1 liver involvement, or stage 1 GI
* Grade III: stage 0-3 skin, with stage 2-3 liver, or stage 2-3 GI
* Grade IV: stage 4 skin, liver or GI involvement

Cookies for Kids' Cancer

St. Jude Children's Research Hospital

Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.

Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses).

Interventions:

* Cycle 1: cytarabine, HPC-A donor infusion
* Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion

Cytarabine: Given by either intrathecal (IT) or intravenous (IV) route.

Intrathecal Triples: given IT.

HPC-A: Given IV.

Myeloid Malignancies

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

This study was terminated in May 2017 due to poor accrual and because of competing protocols.

Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Blinatumomab Plus HLA-Mismatched Cellular Therapy for Relapsed/Refractory CD19+ ALL	NCT03751709	B-Cell Acute Ly... ALL, Adult B-ALL	Blinatumomab Haplo-Mismatche...	18 Years -	Cedars-Sinai Medical Center
Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients	NCT02433483	Acute Myeloid L... Myelodysplastic...	Cytarabine Intrathecal Tri... HPC-A	- 21 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for microtransplant