Methoxyamine and Fludarabine Phosphate in Treating Patients With Relapsed or Refractory Hematologic Malignancies
Phase I Trial of Fludarabine and Methoxyamine (TRC102) for Relapsed or Refractory Hematologic Malignancies
2 other identifiers
interventional
20
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2011
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2011
CompletedFirst Submitted
Initial submission to the registry
July 26, 2012
CompletedFirst Posted
Study publicly available on registry
August 7, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2015
CompletedAugust 13, 2015
August 1, 2015
3.8 years
July 26, 2012
August 12, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD) of methoxyamine given in conjunction with fludarabine in subjects with relapsed or refractory hematologic malignancies
Defined as the highest dose tested in which none or only one subject experiences a dose limiting toxicities attributable to the study drug combination during the first cycle of treatment, when 3-6 subjects were treated at that dose and are evaluable for toxicity.
one cycle (28 days)
MTD of methoxyamine given in conjunction with fludarabine in subjects with relapsed or refractory hematologic malignancies
Defined as the highest dose tested in which none or only one subject experiences a dose limiting toxicities attributable to the study drug combination during the first cycle of treatment, when 3-6 subjects were treated at that dose and are evaluable for toxicity.
after 6 cycles (at 6 months)
Secondary Outcomes (7)
Number of Participants with Adverse Events as a Measure of Dose limiting toxicities of the combination of methoxyamine and fludarabine
at 6 cycles (6 months) of treatment
Number of Participants with Adverse Events as a Measure of Dose limiting toxicities of the combination of methoxyamine and fludarabine
1 year
Pharmacokinetics of methoxyamine when given in combination with fludarabine as determined by methoxyamine levels at different time points.
On day 2, immediately before and 2 hours after the initialmethoxyamine treatment, on days 3-5, and when the patient returns for fludarabine administration and on day 8
Number of apurinic/pyrimidinic (AP) sites.
At 0, 2, 24, 27, 48, 72 and 96 hours post fludarabine-treatment
Change in miRNA profiles in CLL cells in a cohort of CLL patients
Baseline and at 2hrs and 27 hours after treatment
- +2 more secondary outcomes
Study Arms (1)
Treatment (chemotherapy)
EXPERIMENTALPatients receive fludarabine phosphate 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.
Interventions
Given IV
Correlative studies
Correlative studies
Eligibility Criteria
You may qualify if:
- 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
- +8 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Case Comprehensive Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Paolo Caimi, MD
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 26, 2012
First Posted
August 7, 2012
Study Start
May 1, 2011
Primary Completion
February 1, 2015
Study Completion
May 1, 2015
Last Updated
August 13, 2015
Record last verified: 2015-08