DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Methoxyamine and Fludarabine Phosphate in Treating Patients With Relapsed or Refractory Hematologic Malignancies

Information source: Case Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Chronic Lymphocytic Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Intervention: fludarabine phosphate (Drug); methoxyamine (Drug); laboratory biomarker analysis (Other); pharmacological study (Other); western blotting (Genetic); mass spectrometry (Other); DNA analysis (Genetic)

Phase: Phase 1

Status: Completed

Sponsored by: Case Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Paolo Caimi, MD, Principal Investigator, Affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center


This phase I trial is studying the side effects and best dose of methoxyamine when given together with fludarabine phosphate in treating patients with relapsed or refractory hematologic malignancies. Drugs used in chemotherapy, such as methoxyamine and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving methoxyamine together with fludarabine phosphate may kill more cancer cells.

Clinical Details

Official title: Phase I Trial of Fludarabine and Methoxyamine (TRC102) for Relapsed or Refractory Hematologic Malignancies

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Maximum Tolerated Dose (MTD) of methoxyamine given in conjunction with fludarabine in subjects with relapsed or refractory hematologic malignancies

MTD of methoxyamine given in conjunction with fludarabine in subjects with relapsed or refractory hematologic malignancies

Secondary outcome:

Number of Participants with Adverse Events as a Measure of Dose limiting toxicities of the combination of methoxyamine and fludarabine

Number of Participants with Adverse Events as a Measure of Dose limiting toxicities of the combination of methoxyamine and fludarabine

Pharmacokinetics of methoxyamine when given in combination with fludarabine as determined by methoxyamine levels at different time points.

Number of apurinic/pyrimidinic (AP) sites.

Change in miRNA profiles in CLL cells in a cohort of CLL patients

Number of DNA strand breaks determination by comet assay to monitor drug effects on DNA damage in clinical studies.

Measure of Proteins (Bcl-2, Bax, cleaved PARP, Topoisomerase I and II, GammaH2AX)

Detailed description: PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of methoxyamine given in conjunction with fludarabine (fludarabine phosphate) in subjects with relapsed or refractory hematologic malignancies. SECONDARY OBJECTIVES: I. To determine the dose limiting toxicities of the combination of methoxyamine and fludarabine. II. To determine the pharmacokinetics of methoxyamine when given in combination with fludarabine. III. To evaluate pharmacodynamic endpoints including apurinic/apyrimidinic (AP) sites and deoxyribonucleic acid (DNA) strand breaks in blood mononuclear cells to explore the in vivo mechanism of action of methoxyamine and identify the biologically optimal dose to be combined with fludarabine. VI. To determine the disease specific toxicity and biologic activity in a cohort of chronic lymphocytic leukemia (CLL) patients. OUTLINE: This is a dose-escalation study of methoxyamine. Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days 1-5 and methoxyamine IV over 1 hour on day 1 (day 2 of course 1). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 1 year.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- Subjects must have a histologically confirmed hematologic malignancy that has

relapsed or proven refractory (in any time frame) to one or more prior therapies, limited to the following subtypes:

- Non-Hodgkin lymphoma (NHL), including cutaneous lymphoma

- Hodgkin lymphoma (HL)

- Chronic lymphocytic leukemia (CLL)

- Chronic myeloid leukemia (CML)

- Multiple myeloma

- Patients must have progressed through standard curative treatment options in the case

of NHL and HL or not be candidates for curative therapy

- Patients must have measurable disease, and must meet criteria justifying a need to

initiate therapy, criteria for measurable disease and criteria for initiating therapy for purposes of this study are defined as follows:

- NHL/HL: measurable disease by radiographic criteria (>= 1 cm by computed tomography);

or any degree of bone marrow involvement with lymphoma by morphologic analysis; or measurable skin involvement according to cutaneous lymphoma response criteria; criteria for initiating therapy include aggressive histology (diffuse large B cell lymphoma, nodal T cell lymphomas, Hodgkin lymphoma) or presence of any of the following: systemic symptoms, bulk >= 5 cm, >= 3 nodal sites, marrow compromise remaining within limits of adequate function as defined below, splenomegaly >= 16 cm, disease-related effusion, risk of local compressive symptoms, or circulating lymphoma cells

- CLL: measurable disease requires B lymphocytes equal or greater than 5,000/μL, or

lymphadenopathy (>= 1 cm by computed tomography), or bone marrow involvement of any degree; in addition, patients must have one of the following: Rai stage III (hemoglobin < 11gm/dL) or IV (platelets < 100,000/uL) disease, progressive splenomegaly, hepatomegaly or lymphadenopathy, weight loss > 10% over the preceding 6 month period, grade 2 or 3 fatigue, fevers > 100. 5 or night sweats without evidence for infection, progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of < 6 months

- Chronic Myeloid Leukemia: measurable disease requires peripheral or bone marrow

evidence of CML by hematologic, cytogenetic, or molecular analysis; any patient meets criteria for initiating therapy who has failed >= 1 prior treatment with a tyrosine kinase inhibitor (relapsed or refractory)

- Multiple myeloma: measurable disease and presence of end-organ damage; measurable

disease includes any of the following: abnormal free light chain (FLC) ratio, an M-component in the serum or urine, clonal plasma cells in the bone marrow and/or a documented clonal plasmacytoma; end-organ damage includes any of the following: calcium elevation (> 11. 5 mg/dl), anemia (hemoglobin < 10 g/dl), bone disease (lytic lesions or osteopenia), or renal involvement (proteinuria or any known nephropathy) as long as Cr < 1. 5 mg/dL

- Prior chemotherapy and/or radiation are allowed; at least 3 weeks must have elapsed

since prior large-field radiation therapy; patients must have been off previous

anti-cancer therapy for at least 3 weeks. Non - hematologic acute treatment related

toxicities must have resolved to a grade 2 or less, whereas non hematologic chronic treatment related toxicities must be stable or shown improvement in the 4 weeks preceding enrollment. Because of the nature of the diseases treated in this protocol, hematologic toxicities are not included in this criterion and must meet the eligibility criteria described above. At least 12 weeks must have passed since radioimmunotherapy; prior fludarabine treatment is not restricted

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Life expectancy > 12 weeks

- Absolute neutrophil count > 750/ul

- Platelets > 50,000/ul

- Hemoglobin > 9. 0 g/dl

- Total bilirubin < 1. 5 mg/dl

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) <

2. 5 x institutional upper limit of normal

- Creatinine < 1. 5 mg/dl and/or creatinine clearance > 60 mL/min/1. 73 m^2

- Women of childbearing potential and men must agree to use adequate contraception

(hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients may not be receiving any other investigational agents or have received other

investigational agents for at least 3 weeks

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active

infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

- Pregnant and lactating women are excluded from this study

- New York Heart Association (NYHA) classification III or IV heart disease

- Uncontrolled brain or leptomeningeal metastases, including patients who continue to

require glucocorticoids for brain or leptomeningeal metastases

- Known seizure disorder

- Known human immunodeficiency virus (HIV) or chronic hepatitis (B or C) infection

- Patients unwilling or unable for any reason (personal, medical, or psychiatric) to

comply with the protocol

- Patients with known hypersensitivity to fludarabine or a history of purine analog

associated autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura

Locations and Contacts

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, Ohio 44106, United States
Additional Information

Starting date: May 2011
Last updated: August 12, 2015

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017