Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Leukemia

Leukemia, Hairy Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hairy Cell Leukemia

All Drugs and Chemicals

Amino Acids

Tyrosine Kinase Inhibitors

Ibrutinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive ibrutinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Kerry A Rogers

This phase II trial studies how well ibrutinib works in treating patients with hairy cell leukemia that has returned after a period of improvement. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To determine the overall response rate (complete response \[CR\] and partial response \[PR\]) of hairy cell leukemia (HCL) at 32 weeks after beginning therapy with single-agent ibrutinib.

SECONDARY OBJECTIVES:

I. To characterize the toxicity and tolerability of single-agent ibrutinib when administered to patients with HCL.

II. To characterize the progression-free (PFS) and overall survival (OS) of single-agent ibrutinib when administered to patients with HCL.

III. To determine the rate of molecular remission (minimal residual disease \[MRD\]-negative CR) among all patients, defined as resolution of all detectable disease below the limits of detection by immunohistochemistry and/or 4-color flow cytometry assay at 32 weeks after beginning ibrutinib therapy.

IV. To characterize immunologic outcomes during single agent ibrutinib administration.

V. To explore the effect of ibrutinib (PCI-32765) on traditional and new biomarkers in HCL including:

Va. Confirmation of expression BRAFV600E in leukemia cells Vb. Pharmacodynamic effects of BTK inhibition on phosphorylated (phospho) ERK regulation, as well as other potential protein kinase targets of ibrutinib (exploratory) Vc. Serum soluble IL-2 receptor correlation with response to ibrutinib therapy Vd. Documentation of and quantification of minimal residual disease following maximal response, with flow cytometric analysis and immunohistochemical stains of the bone marrow, as predictors of remission duration after ibrutinib therapy.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days for up to 8 cycles if lack of response to therapy, up to 12 cycles if failure to achieve an objective response (CR/PR), or continually at per physician discretion in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia

A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) for Treatment of Relapsed Hairy Cell Leukemia

Computed using non-compartmental and compartmental methods. Graphical analyses will be used as well as repeated measure models (linear or nonlinear mixed models, generalized estimating equation) to assess the PK markers in relation to clinical treatment outcomes.

Calculated as the proportion of patients who achieve a PR or CR to therapy within the first 32 weeks of therapy divided by the total number of evaluable patients.

Frequency and severity of adverse events and tolerability of the regimen in each of the patient groups will be collected and summarized by descriptive statistics and will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Kaplan-Meier curves will be used to estimate overall survival and time to next treatment.

Defined as resolution of all detectable disease below the limits of detection by immunohistochemistry and 4-color flow cytometry assay will be examined.

Markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. responders vs. not). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement.

Pharmacodynamic effects of BTK inhibition on phosphorylated ERK regulation, as well as other possible protein kinase targets of ibrutinib including B lymphoid tyrosine kinase and BMX non-receptor tyrosine kinase/Etk will be assessed.

Will be with flow cytometric analysis and immunohistochemical stains of the bone as predictor of remission duration after ibrutinib therapy.

National Cancer Institute (NCI)

Skin and Connective Tissue Diseases

Mastocytosis

Leukemia, Myeloid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Hematologic Neoplasms

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Mastocytosis, Systemic

Acute Disease

Disease Attributes

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Mast Cell Activation Disorders

Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Systemic Mastocytosis

Dendritic Cell Tumor

Blastic Plasmacytoid Dendritic Cell

Chronic Myeloproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Antipyretics

Analgesics

Antirheumatic Agents

Anti-Allergic Agents

Central Nervous System Depressants

Dermatologic Agents

Anti-Infective Agents

Antibodies

Dexamethasone

Acetaminophen

Ibuprofen

Dexamethasone acetate

BB 1101

Antibodies, Bispecific

Immunoglobulins

Diphenhydramine

Promethazine

Ichthammol

Ranitidine

Ranitidine bismuth citrate

Immunoglobulins, Intravenous

Immunologic Factors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Analgesics, Non-Narcotic

Anti-Inflammatory Agents, Non-Steroidal

Cyclooxygenase Inhibitors

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Antacids

Anti-Ulcer Agents

Histamine H2 Antagonists

INDUCTION THERAPY: Patients receive flotetuzumab via continuous IV infusion on days 1-28. Patients who achieve SD/PR (Cohort A) or PR/CI (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/MMR (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles.

CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

Flotetuzumab

Ibrahim T Aldoss

This phase I trial studies the best dose and side effects of flotetuzumab for the treatment of patients with blood cancers (hematological malignancies) that have spread to other places in the body (advanced) and have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Flotetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (recommended phase 2 dose, RP2D) of flotetuzumab, when given as a single agent.

II. Evaluate the safety and tolerability of flotetuzumab in CD123-positive advanced acute lymphoblastic leukemia (ALL) (Cohort A) and other hematological malignancies (Cohort B), by evaluation of toxicities including: type, frequency, severity, attribution, and duration of the toxicity.

SECONDARY OBJECTIVES:

I. Obtain preliminary estimates of remission; (complete remission \[CR\], complete remission with incomplete count recovery \[CRi\], complete remission with partial hematological recovery \[CRh\] or morphologic leukemia free state \[MLFS\] in Cohort A or CR/molecular response \[MR\] in Cohort B) rate and duration.

II. Estimate 1-year overall survival. III. Evaluate minimal residual disease (MRD) status in responders in the ALL cohort.

IV. Evaluate the percentage of patients who receive subsequent allogeneic transplantation.

EXPLORATORY OBJECTIVES:

I. Examine immune profile pre- and post-treatment with flotetuzumab. II. Assess the association between CD123 expression and tumor response. III. Assess the association between alterations in tumor genetic or microenvironment with response.

IV. Assess cytokine levels during therapy.

OUTLINE: This is a dose-escalation study.

INDUCTION THERAPY: Patients receive flotetuzumab via continuous intravenous (IV) infusion on days 1-28. Patients who achieve stable disease (SD)/partial remission (PR) (Cohort A) or PR/clinical improvement (CI) (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/major molecular response (MMR) (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles.

CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

SUPPORTIVE CARE: Patients also receive acetaminophen orally (PO) or ibuprofen PO every 8 hours for 48 hours, diphenhydramine or equivalent IV or PO every 8 hours for 48 hours, ranitidine or equivalent IV every 8 hours for 48 hours, and dexamethasone IV up to 30 minutes prior to dosing and then at 12 hours after dosing on week 1 days 1 and 7.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.

Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies

A Phase 1 Trial to Evaluate the Safety of Single Agent Flotetuzumab in Advanced CD123-Positive Hematological Malignancies

Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0 except infusion-related reaction (IRR)/cytokine release syndrome (CRS) which will be by the modified criteria proposed by Lee et al. Safety and toxicity will be assessed for each cohort independently. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, probable association with the study treatment and reversibility or outcome.

Rates and 95% Clopper Pearson binomial confidence interval (CI) will be calculated for complete remission/response rate (confirmed complete remission \[CR\]/ complete remission with incomplete count recovery \[CRi\]/ complete remission with partial hematological recovery \[CRh\] \[Cohort A\] or CR/molecular response \[MR\] \[Cohort B\]). Remission rates will also be explored based on number/type of prior therapy(ies), the presence of extramedullary disease at the time of starting therapy, disease burden, and CD123 expression intensity.

Assessed by multi-color flow cytometry in ALL the cohorts.

Will be estimated using the product-limit method of Kaplan and Meier.

Number/percent of patients who proceed to hematopoietic cell transplantation after achieving complete response/ complete remission

City of Hope Medical Center

Antibodies, Monoclonal

Rituximab

Cladribine

2-chloro-3'-deoxyadenosine

Antineoplastic Agents, Immunological

2'-deoxyadenosine

Cordycepin

Immunosuppressive Agents

Antimetabolites

Patients receive cladribine IV over 2 hours QD on days 1-5 and rituximab IV once weekly for 8 weeks beginning on day 28 in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Farhad Ravandi-Kashani

Farhad Ravandi-Kashani, MD

This phase II trial studies the side effects and how well cladribine and rituximab work in treating patients with hairy cell leukemia. Drugs used in chemotherapy, such as cladribine, 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. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cladribine together with rituximab may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To demonstrate the efficacy in achieving complete response of combination of cladribine administered intravenously over 2 hours for 5 days followed by rituximab weekly for 8 weeks in patients with untreated or previously treated hairy cell leukemia.

II. To examine the efficacy of rituximab to eradicate minimal residual disease (MRD) after cladribine therapy (as assessed by immunophenotyping of bone marrow and peripheral blood).

III. To examine the effect of addition of rituximab to cladribine on the long term disease-free (DFS) and overall survival (OS) (as compared with historical controls).

IV. To evaluate potential predictors of outcome including molecular and flow evaluations of MRD, as well as other potential molecular predictors such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF).

OUTLINE:

Patients receive cladribine intravenously (IV) over 2 hours once daily (QD) on days 1-5 and rituximab IV once weekly for 8 weeks beginning on day 28 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Cladribine and Rituximab in Treating Patients With Hairy Cell Leukemia

Phase II Study of 2-Chlorodeoxyadenosine (2CDA) Followed by Rituximab in Hairy Cell Leukemia

Defined as the absence of hairy cells in the bone marrow or the presence of less than 1 percent atypical cells and the disappearance of all evidence of hairy cell leukemia on physical examination. Monitored using the method of Thall, Simon, Estey as extended by Thall and Sung.

Monitored using the method of Thall, Simon, Estey as extended by Thall and Sung.

The method of Thall, Simon, Estey as extended by Thall and Sung will be used for efficacy and safety monitoring.

M.D. Anderson Cancer Center

Venetoclax

Patients receive venetoclax PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or aspiration on study.

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Computed Tomography

Magnetic Resonance Imaging

Robert J Kreitman

This phase II trial tests how well venetoclax works in treating patients with hairy cell leukemia that has come back after a period of improvement (relapsed). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival.

PRIMARY OBJECTIVE:

I. To determine the objective response rate (ORR) of venetoclax.

SECONDARY OBJECTIVES:

I. To determine the complete remission (CR) and minimal residual disease (MRD)-negative CR rates of venetoclax in relapsed hairy cell leukemia/hairy cell leukemia variant (HCL/HCLv).

II. To determine the rates of MRD-negative by blood flow cytometry with venetoclax.

III. To determine the safety of venetoclax in relapsed HCL/HCLv. IV. To determine the response and CR duration and MRD-negative survival in relapsed HCL/HCLv receiving venetoclax.

EXPLORATORY OBJECTIVES:

I. To correlate response to TP53 mutations and other mutations, particularly for BRAF wild-type (WT) relapsed HCL/HCLv.

II. To perform whole exome sequencing (WES) of relapsed HCL/HCLv samples to look for mutations, to correlate with response.

OUTLINE:

Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or aspiration on study.

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

Venetoclax for the Treatment of Patients With Relapsed Hairy Cell Leukemia

A Phase 2 Study of Venetoclax in Relapsed Classic or Variant Hairy Cell Leukemia

"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

Will correlate response to TP53 mutations and other mutations.

Will perform whole exome sequencing of relapsed HCL/HCLv samples to look for mutations, to correlate with response.

Will be determined with 95% confidence intervals for each group.

CR will be defined as resolution of cytopenias with neutrophils \> 1.5/nL, platelets \> 100/nL, and hemoglobin \> 11g/dL at least 4 weeks from last transfusion or growth factor, resolution of splenomegaly by exam or by spleen size \< 17 cm by imaging, resolution of hairy cell leukemia (HCL)/hairy cell leukemia variant (HCLv)-related lymphadenopathy/masses to \< 2cm in short axis (\< 0.5 cm in short axis in the central nervous system \[CNS\]), and absence of morphological evidence of HCL/HCLv in the blood and bone marrow.

Defined as meeting the criteria for CR plus absence of HCL/HCLv cells in the bone marrow aspirate and blood by flow cytometry, and negative immunochemistry of the bone marrow biopsy. Positive IHC involves B-cells \> T-cells and most of the B-cells being consistent with HCL. Patients with CNS disease who achieve CR with positive cerebrospinal fluid flow cytometry will be considered CR with MRD.

Will determine the rates of MRD-negative by blood flow cytometry.

Heart and Blood Diseases

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Lymphoma, Non-Hodgkin

Leukemia, B-Cell

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

B-cell Lymphoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

Indolent B Cell Lymphoma

Azacitidine

Obinutuzumab

Lenalidomide

Cc-486

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive azacitidine PO QD on days 1-21, obinutuzumab IV over on days 8, 15, 22, and 29, and lenalidomide PO QD on days 8-28 of cycle 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Patients then receive azacitidine PO QD on days 1-21, obinutuzumab IV over on day 1, and lenalidomide PO QD on days 1-21. Cycles repeats every 28 days in the absence of disease progression, unacceptable toxicity, or until stem cell transplant. Patients who achieve SD, PR, or CR do not proceed to stem cell transplant may continue treatment for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Oral Azacitidine

Joseph M Tuscano

This phase I/Ib trial investigates the side effects of CC-486 and how well it works in combination with lenalidomide and obinutuzumab in treating patients with CD20 positive B-cell lymphoma that has come back (recurrent) or has not responded to treatment (refractory). Chemotherapy drugs, such as CC-486, 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. Lenalidomide is a drug that alters the immune system and may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Obinutuzumab is a type of antibody therapy that targets and attaches to the CD20 proteins found on follicular lymphoma cells as well as some healthy blood cells. Once attached to the CD20 protein the obinutuzumab is thought to work in different ways, including by helping the immune system destroy the cancer cells and by destroying the cancer cells directly. Giving CC-486 with lenalidomide and obinutuzumab may improve response rates, quality, and duration, and minimize adverse events in patients with B-cell lymphoma.

PRIMARY OBJECTIVE:

To assess the safety and toxicity of oral azacitidine (CC-486) in combination with lenalidomide and obinutuzumab.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of CC-486 in combination with lenalidomide and obinutuzumab in subjects with relapsed/refractory indolent B-cell lymphoma as assessed by:

Ia. Overall response rate: complete response (CR) + partial response (PR) per 2016 Lugano criteria and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.

Ib. Duration of response (DOR): will be calculated from time of initial response assessment demonstrating at least PR until disease response assessment that demonstrates progressive disease.

Ic. Time to response (TTR): calculated as time from registration to first disease response assessment that demonstrates at least PR.

Id. Progression-free survival (PFS): Patients are considered a failure for this endpoint if they die or if they relapse/progress or receive additional anti-lymphoma therapy.

Ie. Determine the recommended phase 2 dose (RP2D).

CC-486, Lenalidomide, and Obinutuzumab for the Treatment of Recurrent or Refractory CD20 Positive B-cell Lymphoma

A Phase I/IB Pilot Study of CC-486 Combined With Lenalidomide and Obinutuzumab for Relapsed/Refractory Indolent B-Cell Lymphoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ibrutinib in Treating Patients With Relapsed Hairy Cell Leukemia	NCT01841723	Hairy Cell Leuk... Hairy Cell Leuk... Recurrent Hairy...	Ibrutinib	18 Years -	National Cancer Institute (NCI)
Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies	NCT04681105	Recurrent Acute... Recurrent B Acu... Recurrent Blast... Recurrent Chron... Recurrent Hairy... Recurrent Hemat... Recurrent Hodgk... Recurrent T Acu... Refractory Acut... Refractory B Ac... Refractory Blas... Refractory Chro... Refractory Hair... Refractory Hema... Refractory Hodg... Refractory T Ac... Systemic Mastoc...	Acetaminophen Dexamethasone Diphenhydramine Flotetuzumab Ibuprofen Ranitidine	12 Years -	City of Hope Medical Center
Cladribine and Rituximab in Treating Patients With Hairy Cell Leukemia	NCT00412594	Hairy Cell Leuk... Recurrent Hairy...	Cladribine Laboratory Biom... Rituximab	18 Years -	M.D. Anderson Cancer Center
Venetoclax for the Treatment of Patients With Relapsed Hairy Cell Leukemia	NCT06311227	Recurrent Hairy... Recurrent Hairy...	Biospecimen Col... Bone Marrow Asp... Bone Marrow Bio... Computed Tomogr... Magnetic Resona... Venetoclax	18 Years -	National Cancer Institute (NCI)
CC-486, Lenalidomide, and Obinutuzumab for the Treatment of Recurrent or Refractory CD20 Positive B-cell Lymphoma	NCT04578600	Indolent B-Cell... Recurrent B-Cel... Recurrent Chron... Recurrent Mucos... Recurrent Folli... Recurrent Hairy... Recurrent Lymph... Recurrent Mantl... Recurrent Margi... Refractory B-Ce... Refractory Chro... Refractory Muco... Refractory Foll... Refractory Hair... Refractory Lymp... Refractory Mant... Refractory Marg... Recurrent Small... Refractory Smal...	Lenalidomide Obinutuzumab Oral Azacitidin...	18 Years -	University of California, Davis

Spots Global Cancer Trial Database for recurrent hairy cell leukemia