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New treatment option for Lymphoma, T-Cell
Official title Durvalumab in Different Combinations With Pralatrexate, Romidepsin and Oral 5-Azacitidine for Lymphoma
ClinicalTrials.gov ID: NCT03161223
What this study is testing
What is Durvalumab?
Durvalumab is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for lymphoma, t-cell.
Also referred to as MEDI4736.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This is an open-label, Phase 1/2a, dose-finding study with an initial phase 1 portion, articulated in four separate treatment arms, followed by a dedicated phase 2 for qualifying treatment Arm(s). The primary objective of the Phase 1 portion is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of: Durvalumab, oral 5-azacitidine, and romidepsin (Arm A); durvalumab, pralatrexate, and romidepsin (Arm B); durvalumab and romidepsin (Arm C); or durvalumab and oral 5-azacitidine (Arm D), in patients with peripheral T-cell lymphoma (PTCL).
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- (these criteria apply to both the phase 1 and phase 2 portion of the study)
- Age \>18 years at the time of signing the informed consent
- Patients must have histologically confirmed newly diagnosed (ND) or Relapsed/Refractory Peripheral T-Cell Lymphoma (R/R PTCL) defined according to...
- Patients with R/R PTCL who have received at least one previous line of therapy are eligible to be enrolled in this study.
- Patients who are candidate for an autologous or allogeneic stem cell transplantation (SCT) will be allowed to receive the study drugs as a "bridge"...
You likely can't join if
- (these criteria apply to both the phase 1 and phase 2 portion of the study)
- Prior Therapy (for patients with R/R PTCL)
- Exposure to any agent targeting PD-1, PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
- For three-drug combinations, the patient must not have been exposed to at least two of those drugs. For two drugs combinations patients must not have...
- Exposure to biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation therapy within 2 weeks prior to...
- Current or prior use of immunosuppressive medication within 14 days prior to first dose of durvalumab. The following are exceptions to this...
See the full eligibility criteria
Who can join
- (these criteria apply to both the phase 1 and phase 2 portion of the study)
- Age \>18 years at the time of signing the informed consent
- Patients must have histologically confirmed newly diagnosed (ND) or Relapsed/Refractory Peripheral T-Cell Lymphoma (R/R PTCL) defined according to the 2016 World Health Organization (WHO) classification criteria.
- Patients with R/R PTCL who have received at least one previous line of therapy are eligible to be enrolled in this study.
- Patients who are candidate for an autologous or allogeneic stem cell transplantation (SCT) will be allowed to receive the study drugs as a "bridge" to transplantation.
- Evaluable (phase 1) or measurable (phase 2) disease.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Patients must have adequate organ and marrow function as defined by:
- Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2 x institutional upper limit of normal (ULN); total bilirubin ≤ 1.5 x ULN (AST, ALT, and total bilirubin ≤ 3 × ULN in people with documented...
- Creatinine levels \ 40 mL/min
- Absolute neutrophil count (ANC) \> 1,000/μL; platelet count \> 75,000/μL
- Negative urine or serum pregnancy test for women of childbearing potential. All women of childbearing potential must agree to use an effective barrier method of contraception (either an intrauterine device (IUD) or...
- Ability to understand and the willingness to sign a written informed consent document.
- Ability to adhere to the study visit schedule and other protocol requirements
What rules you out
- (these criteria apply to both the phase 1 and phase 2 portion of the study)
- Prior Therapy (for patients with R/R PTCL)
- Exposure to any agent targeting PD-1, PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
- For three-drug combinations, the patient must not have been exposed to at least two of those drugs. For two drugs combinations patients must not have been exposed to any of those drugs. Patients will be enrolled in the...
- Exposure to biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation therapy within 2 weeks prior to entering the study or lack of resolution of AE due to previously administered...
- Current or prior use of immunosuppressive medication within 14 days prior to first dose of durvalumab. The following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (e.g...
- Prior allogeneic SCT
- History of, or suspected allergic reactions to, durvalumab, pralatrexate, oral 5-azacitidine, or romidepsin or any of their excipients.
- For patients who are treated with oral 5-azacitidine, any gastrointestinal disorder that would interfere with the absorption of the study drug
- Concomitant use of CYP3A4 inhibitors
- Uncontrolled intercurrent illness.
- Any of the following cardiac abnormalities (only for patients receiving romidepsin):
- Congenital long QT syndrome;
- corrected QT (QTc) interval ≥ 501 milliseconds;
- Patients taking drugs leading to significant QT prolongation (See Appendix 3);
- Myocardial infarction within 6 months of cycle 1, day 1. [people with a history of myocardial infarction between 6 and 12 months prior to cycle 1, day 1, who are asymptomatic and have had a negative cardiac risk...
- Other significant 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...
- 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...
- Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions (see Appendix 5) and/or ejection fraction \< 40% by multitargeted acquisition (MUGA) scan or \< 50% by...
- A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);
- 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...
- Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers).
- Pregnancy or breast-feeding.
- 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...
- Receipt of solid organ transplant.
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis with the exception of a prior episode that has resolved or...
- Central nervous system (CNS) involvement, including lymphomatous meningitis.
- Known active hepatitis A, B or C virus infection.
- Known HIV infection.
- History of primary immunodeficiency.
- Receipt of live, attenuated vaccine within 30 days prior to study entry. Enrolled patients should not receive live vaccine during the study and 30 days after the last dose of durvalumab.
The study team makes the final eligibility decision.
Where it's taking place
- Charlottesville, Virginia, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Charlottesville, Virginia, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.