Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Neoplasms

Heart and Blood Diseases

Rare Diseases

Philadelphia Chromosome

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Translocation, Genetic

Chromosome Aberrations

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

Rona S Weinberg, PhD

John Mascarenhas, MD

Researchers will use abnormal blood and/or bone marrow cells, or materials derived from these abnormal cells, like DNA, RNA, protein or plasma, in laboratory studies. Toenail clippings will provide normal material like DNA for comparison with the abnormal material derived from the blood and/or bone marrow. The results of these studies will be correlated with subjects' disease symptoms and response to their experimental treatment. The MPD-RC researchers are interested in studying molecules from the blood and bone marrow, the exact molecules changing over time with the investigators choosing only the most promising for investigation.

The investigators are attempting to better understand the causes of MPD and to develop improved methods for the diagnosis and treatment of these diseases. These syndromes carry a high risk of developing leukemia. It is important to continue to learn more about these blood cancers and to learn more about the effectiveness and potential side effects of various treatments. It is believed that further basic knowledge about these cancer cells as well as the effects of treatment will lead to the improvement of current therapies and the development of entirely new treatments for these diseases. The MPD-RC is hoping to determine if a number of laboratory tests (biomarkers) will allow for the prediction of response in future patients to the treatment they would receive.

Leftover tissue will be asked for to be stored in the MPD-RC Tissue Bank

Correlative Biomarker Study in Patients With Myeloproliferative Disorders

Correlative Biomarker Study for MPD-RC Treatment Studies in the Philadelphia Chromosome Negative MPD

Myeloproliferative Disorders-Research Consortium

National Cancer Institute (NCI)

Icahn School of Medicine at Mount Sinai

Immune System Diseases

Recurrence

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Micronutrients

Dermatologic Agents

Reproductive Control Agents

Hematinics

Bone Density Conservation Agents

Vitamins

Antibodies

Antibodies, Monoclonal

Cytarabine

Cyclophosphamide

Dexamethasone

Leucovorin

Levoleucovorin

Methotrexate

Rituximab

Vincristine

Calcium

Lenograstim

Dexamethasone acetate

BB 1101

Folic Acid

Immunoglobulins

Blinatumomab

Mercaptopurine

Calcium, Dietary

Muromonab-CD3

Ichthammol

Vitamin B Complex

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Antibodies, Bispecific

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Antimetabolites

Folic Acid Antagonists

Antiviral Agents

Adjuvants, Immunologic

Antidotes

Protective Agents

Trace Elements

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Filgrastim

Laboratory Biomarker Analysis

Leucovorin Calcium

Pegfilgrastim

Vincristine Sulfate

Elias Jabbour

This phase II trial studies how well low-intensity chemotherapy and blinatumomab work in treating patients with Philadelphia chromosome negative acute lymphoblastic leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as dexamethasone, filgrastim, pegfilgrastim, cyclophosphamide, methotrexate, cytarabine and vincristine sulfate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving low-intensity chemotherapy and blinatumomab may work better at treating acute lymphoblastic leukemia.

PRIMARY OBJECTIVE:

I. To evaluate the combined effect of blinatumomab and mini-hyper-CVD (low-intensity chemotherapy) on event-free survival.

SECONDARY OBJECTIVES:

I. Evaluating other clinical efficacy endpoints (minimal residual disease \[MRD\] negativity, duration of response, the overall response rate \[complete response (CR) + CR with inadequate count recovery (CRi)\]) of the regimen occurred any time during the treatment.

II. Overall survival. III. Determining the safety of the combination regimen.

OUTLINE:

INDUCTION PHASE: Patients receive blinatumomab intravenously (IV) continuously on days 1-28 and dexamethasone orally (PO) or IV over 30 minutes on days -3 to day 0 and 7-10. Patients also receive filgrastim subcutaneously (SC) on days 1-42 or pegfilgrastim SC on days 1 and 25, cyclophosphamide IV over 3 hours twice daily (BID) on days -3 to -1, methotrexate intrathecally (IT) on day 2 and IV over 24 hours on day 22, cytarabine IT on day 7 and IV over 3 hours BID on days 23 and 24, and vincristine sulfate IV over 15 minutes on days 0 and 7. At the discretion of the treating physician, patients may receive rituximab IV over 4-6 hours on days -3, 0, 22 and 29, and leucovorin calcium IV over 15 minutes or PO 4 times daily (QID) for 8 doses.

CONSOLIDATION PHASE: Patients receive blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV over 30 minutes on days 1-4 and 11-14. Patients also receive cyclophosphamide IV over 3 hours BID on days 1-3, vincristine sulfate IV over 15 minutes on days 1 and 11, filgrastim SC on days 1-4 and 22-42 or pegfilgrastim SC on day 5 and 25, methotrexate IT on day 2 and IV over 24 hours on day 22, cytarabine IT on day 7 and IV over 3 hours BID on days 23 and 24. At the discretion of the treating physician, patients may receive rituximab IV over 4-6 hours on days 1, 8, 22 and 29, and leucovorin calcium IV over 15 minutes or PO QID for 8 doses. Treatment repeats every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive prednisone PO and vincristine sulfate IV over 15 minutes on days 1-5 of cycles 5-9, 7-11 and 13-24, and mercaptopurine PO BID on days 1-28 of cycles 1-5, 7-11, and 13-24. Patients also receive methotrexate PO once a week and blinatumomab IV continuously on days 1-28 of cycles 6 and 12. Cycles repeat every 28 days for up to 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Low-Intensity Chemotherapy and Blinatumomab in Treating Patients With Philadelphia Chromosome Negative Relapsed or Refractory Acute Lymphoblastic Leukemia

Phase II Study of the Combination of Low-Intensity Chemotherapy and Blinatumomab in Patients With Philadelphia Chromosome Negative Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

Time from date of treatment start until the date of first objective documentation of disease-relapse. Relapse and resistant disease will be defined based on morphological assessment of bone marrow and peripheral blood.

Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10\^9/L or above, and platelet count of 100 x 10\^9/L. Complete resolution of all sites of extramedullary disease is required for CR.

Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets \< 100 x 10\^9/L; neutrophils \< 1 x 10\^9/L).

Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts.

Minimal Residual Disease (MRD) was assessed by flow cytometry. MRD negativity: Absence of detectable leukemia using multiparameter flow cytometry with a sensitivity of \</= 0.01%.

Response date to loss of response or last follow up. Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10\^9/L or above, and platelet count of 100 x 10\^9/L. Complete resolution of all sites of extramedullary disease is required for CR.

Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets \< 100 x 10\^9/L; neutrophils \< 1 x 10\^9/L).

Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts.

defined as the percentage of patients achieving complete response (CR) or CR with inadequate count recovery (CRi). Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10\^9/L or above, and platelet count of 100 x 10\^9/L. Complete resolution of all sites of extramedullary disease is required for CR.

Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets \< 100 x 10\^9/L; neutrophils \< 1 x 10\^9/L).

Time from date of treatment start until date of death due to any cause or last Follow-up.

M.D. Anderson Cancer Center

See detailed description.

Blinatumomab: Given IV

Cyclophosphamide: Given IV

Cytarabine: Given IT or IV

Dexamethasone: PO or IV

Filgrastim: Given SC

Laboratory Biomarker Analysis: Correlative studies

Leucovorin Calcium: Given IV

Mercaptopurine: Given PO

Methotrexate: Given IT or IV

Pegfilgrastim: Given SC

Rituximab: Given IV

Vincristine Sulfate: Given IV

Treatment (Blinatumomab, Combination Chemotherapy)

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Elias Joseph Jabbour MD/Professor

Event Free Survival (EFS) Where Events Defined as no Response, Loss of Response, or Death

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Correlative Biomarker Study in Patients With Myeloproliferative Disorders	NCT00665067	Myeloproliferat... Myelofibrosis Idiopathic Myel... Essential Throm... Polycythemia Ve...		18 Years -	Icahn School of Medicine at Mount Sinai
Correlative Biomarker Study in Patients With Myeloproliferative Disorders	NCT00665067	Myeloproliferat... Myelofibrosis Idiopathic Myel... Essential Throm... Polycythemia Ve...		18 Years -	Icahn School of Medicine at Mount Sinai
Low-Intensity Chemotherapy and Blinatumomab in Treating Patients With Philadelphia Chromosome Negative Relapsed or Refractory Acute Lymphoblastic Leukemia	NCT03518112	Philadelphia Ch... Recurrent B Acu... Refractory B Ac...	Blinatumomab Cyclophosphamid... Cytarabine Dexamethasone Filgrastim Laboratory Biom... Leucovorin Calc... Mercaptopurine Methotrexate Pegfilgrastim Rituximab Vincristine Sul...	18 Years -	M.D. Anderson Cancer Center
Low-Intensity Chemotherapy and Blinatumomab in Treating Patients With Philadelphia Chromosome Negative Relapsed or Refractory Acute Lymphoblastic Leukemia	NCT03518112	Philadelphia Ch... Recurrent B Acu... Refractory B Ac...	Blinatumomab Cyclophosphamid... Cytarabine Dexamethasone Filgrastim Laboratory Biom... Leucovorin Calc... Mercaptopurine Methotrexate Pegfilgrastim Rituximab Vincristine Sul...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for philadelphia chromosome negative