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Leflunomide in Treating Patients With Relapsed or Refractory Multiple Myeloma

Information source: City of Hope Medical Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Intervention: Laboratory Biomarker Analysis (Other); Leflunomide (Drug); Pharmacological Study (Other)

Phase: Phase 1

Status: Not yet recruiting

Sponsored by: City of Hope Medical Center

Official(s) and/or principal investigator(s):
Michael Rosenzweig, Principal Investigator, Affiliation: City of Hope Medical Center

Summary

This phase I trial studies the side effects and best dose of leflunomide in treating patients with multiple myeloma that has come back (recurrent) or has not responded to previous treatment (refractory). Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Clinical Details

Official title: A Phase I Dose-Escalation Trial of Leflunomide in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma

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

Primary outcome:

Incidence of toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

MTD, defined as the highest dose in which =< 1/6 patients experience a dose-limiting toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

Secondary outcome:

Best overall response, (stringent complete response [sCR]/complete response [CR]/very good partial response [VGPR]/or partial response [PR])

Clinical benefit response, defined as the best response (sCR/CR/VGPR/minimal response [MR] or stable disease [SD]) recorded

Overall survival

Progression-free survival

Response duration

Response, categorized using the International Myeloma Working Group (IMWG) criteria for multiple myeloma

Detailed description: PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of leflunomide, when given as a single agent, in patients with relapsed or relapsed/refractory multiple myeloma. II. To assess the safety and tolerability of leflunomide at each dose level by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. SECONDARY OBJECTIVES: I. To characterize the relationship between serum concentration of the active leflunomide metabolite, teriflunomide (A771726) and toxicity. II. To characterize any clinical activity of leflunomide by assessing: disease response, response duration, and clinical benefit response. III. To assess the relationship between serum concentration of the active leflunomide metabolite (teriflunomide) and disease response. IV. To obtain estimates of overall and progression-free survival. V. To explore the relationship between gene polymorphisms in the gene encoding dihydroorotate dehydrogenase (DHODH) and toxicity/response. OUTLINE: This is a dose-escalation study. Patients receive leflunomide orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 28 days until disease progression (active follow-up) or every 3 months (long term follow-up).

Eligibility

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

Criteria:

Inclusion Criteria:

- All subjects must have the ability to understand and the willingness to sign a

written informed consent

- Patients must have a life expectancy of > 3 months

- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status

of 0-2

- Patients must have a diagnosis of multiple myeloma

- Serum M-protein >= 0. 5 g/dL

- Urine M-protein >= 200 mg/24 hr

- Serum free light chain >=10 mg/dL provided the free light chain (FLC) ratio is

abnormal

- Patients must be refractory or relapsed after 2 prior regimens (induction therapy and

stem cell transplant +/- maintenance will be considered as one regimen)

- At least 2 weeks from prior therapy to time of start of treatment; prior therapy

includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed)

- Platelet count >= 50,000/uL; platelet transfusions are not allowed within 14 days of

platelet assessment

- Absolute neutrophil count (ANC) >= 1000/mm^3; growth factor is not permitted within

14 days of neutrophil assessment

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2. 0 x ULN

- Calculated creatinine clearance (CrCl) >= 30 mL/min per 24 hour urine collection or

the Cockcroft-Gault formula

- Negative serum or urine beta-human chorionic gonadotropin (B-HCG) test (female

patient of childbearing potential* only), to be performed locally within the screening period

- Negative for tuberculosis antigen (e. g. T-Spot test)

- Negative for hepatitis A, B, or C infection

- Adequate pulmonary function as defined by forced vital capacity (FVC) and carbon

monoxide diffusing capacity (DLCO) >= 50% of predicted by pulmonary function testing

- Agreement by females of childbearing potential* and sexually active males to use an

effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

- A female of childbearing potential is defined as a sexually mature woman who: 1)

has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months Exclusion Criteria:

- Prior treatment with leflunomide

- Current or planned use of other investigational agents, or concurrent biological,

chemotherapy, or radiation therapy during the study treatment period

- Current or planned growth factor or transfusion support until after initiation of

treatment; if growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible

- Prior diagnosis of rheumatoid arthritis

- Acute active infection requiring systemic therapy within 2 weeks prior to enrollment

- Pre-existing liver disease

- Known human immunodeficiency virus (HIV) infection

- History of allergic reactions attributed to compounds of similar chemical or biologic

composition to leflunomide or cholestyramine

- Non-hematologic malignancy within the past 3 years aside from the following

exceptions:

- Adequately treated basal cell or squamous cell skin cancer

- Carcinoma in situ of the cervix

- Prostate cancer < Gleason grade 6 with a stable prostate specific antigen (PSA)

- Successfully treated in situ carcinoma of the breast

- Clinically significant medical disease or condition that, in the investigator's

opinion, may interfere with protocol adherence or the patient's ability to give informed consent

- Pregnant women and women who are lactating; breastfeeding should be discontinued if

the mother is enrolled on this study

- Any other condition that would, in the investigator's judgment, contraindicate the

patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e. g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc

- NONCOMPLIANCE: Prospective participants who, in the opinion of the investigator, may

not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Locations and Contacts

City of Hope Medical Center, Duarte, California 91010, United States; Not yet recruiting
Michael A. Rosenzweig, Phone: 626-256-4673, Email: mrosenzweig@coh.org
Michael A. Rosenzweig, Principal Investigator
Additional Information

Starting date: December 2015
Last updated: July 23, 2015

Page last updated: August 20, 2015

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