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Pralatrexate and Romidepsin in Treating Patients with Relapsed or Refractory Lymphoma or Multiple Myeloma

Trial Status: Active

This phase I / IIa trial studies the side effects and the best dose of pralatrexate and romidepsin and to see how well they work in treating patients with lymphoma or multiple myeloma that has come back after a period of improvement or does not respond to treatment. Pralatrexate may slow, stop, or decrease the growth of cancer cells by blocking how cells are made. Romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pralatrexate together with romidepsin may work better in treating patients with non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma

Inclusion Criteria

  • Patients must have histologically confirmed relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease (World Health Organization [WHO] criteria) (Phase I)
  • Patients with T-cell lymphoma (untreated, relapsed or refractory) (Phase II)
  • There is no upper limit for the number of prior therapies; patients may have relapsed after prior autologous or allogeneic stem cell transplant
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count >= 1,000/dL
  • Platelets >= 75,000 total
  • Bilirubin =< 1.5 x institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x institutional upper limit of normal; or < 3.0 X upper limit of normal (ULN) in presence of demonstrable liver involvement
  • Serum creatinine < 2 x institutional upper limit of normal OR creatinine clearance >= 50 mL/min/for patients with creatinine levels above institutional normal
  • Negative urine or serum pregnancy test for females of childbearing potential
  • All females of childbearing potential must use an effective barrier method of contraception (either an intrauterine device contraceptive [IUDC] or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter; male subjects should use a barrier method of contraception during the treatment period and for at least 3 months thereafter; female subjects should avoid the use of estrogen-containing contraceptives
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Exposure to chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
  • Systemic steroids that have not been stabilized to the equivalent of =< 10 mg/day prednisone prior to the start of the study drugs
  • No other concurrent investigational agents are allowed
  • Central nervous system metastases, including lymphomatous meningitis
  • History of allergic reactions to pralatrexate or romidepsin
  • 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 women
  • Nursing women
  • Active concurrent malignancy (except non-melanoma skin cancer, prostatic intraepithelial neoplasia, or carcinoma in situ of the cervix); patients whose lymphoma has transformed from a less aggressive histology remain eligible
  • Patients known to be human immunodeficiency virus (HIV)-positive
  • Patients with active hepatitis A, hepatitis B, or hepatitis C infection
  • Concomitant use of CYP3A4 inhibitors
  • Any known cardiac abnormalities such as: * Congenital long QT syndrome * Corrected QT (QTc) interval >= 500 milliseconds * Patients taking drugs leading to significant QT prolongation * Myocardial infarction within 6 months of cycle1 day 1 (C1D1); (subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate) * Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) * Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present * An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present * Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multi gated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI) * A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest * Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes * Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria or * Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
  • Untreated ALK+ anaplastic large cell lymphoma (ALCL)
  • Untreated cutaneous T-Cell non-Hodgkin lymphoma (CTCL) (with the exception of untreated tumor stage Mycosis fungoides)


Beth Israel Deaconess Medical Center
Status: ACTIVE
Contact: Salvia Jain

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE
Contact: Jennifer Effie Amengual
Phone: 212-326-5720


Fox Chase Cancer Center
Status: ACTIVE
Contact: Stefan Klaus Barta


I. Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combination of pralatrexate and romidepsin. (Phase I)

II. Evaluate the safety and toxicity of the combinations of pralatrexate and romidepsin. (Phase I)

III. Estimate the overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with T-cell lymphoma (untreated, relapsed or refractory). (Phase II)


I. Describe the maximum number of cycles received. (Phase I)

II. Describe the number of dose delays and dose reductions at the MTD. (Phase I)

III. Describe the anti-tumor activity of the combination. (Phase I)

IV. Evaluate the overall response rate (ORR), progression free survival (PFS), and duration of response (DOR) of the study population. (Phase I)

V. Evaluate pharmacodynamic markers of drug effect in paired tissue biopsies (pre- and post- treatment), including reduced folate carrier 1(RFC-1), adenosine triphosphate (ATP)-binding cassette, sub-family G (WHITE), member 2 (ABCG2), folylpolyglutamyl synthase (FPGS), gamma-glutamyl hydrolase (GGH), dihydrofolate reductase (DHFR). (Phase I)

VI. Evaluate the pharmacokinetic profile for pralatrexate and romidepsin when given as a combination in cycle 1 day 1 at various time intervals. (Phase I)

VII. Estimate the DOR and PFS of the combination in patients with T-cell lymphoma. (Phase II)

VIII. Estimate the overall survival of patients with T-cell lymphoma on study. (Phase II)

IX. Identify potential pre-treatment biomarkers of response (RFC, FPGS) to clinical outcome. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive romidepsin intravenously (IV) over 4 hours and pralatrexate IV over 3-5 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3-6 months for 1 year.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Jennifer Effie Amengual

  • Primary ID AAAJ5656
  • Secondary IDs NCI-2014-01986
  • ID NCT01947140