Pentamidine + Salvage Chemo for Relapsed/Refractory Classical Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT03730363|
Recruitment Status : Recruiting
First Posted : November 5, 2018
Last Update Posted : December 20, 2018
To evaluate dose limiting toxicity and to determine the recommended phase 2 dose (RP2D) of pentamidine in combination with salvage chemotherapy with ifosfamide, carboplatin and etoposide (ICE) on a 3-weeks schedule in relapsed/refractory classical Hodgkin lymphoma (cHL).
- To estimate the overall best treatment response at 5- and 16-weeks from study enrollment. Although the clinical benefit of these drugs in combination has not been established, offering this treatment may provide a therapeutic benefit. The patients will be carefully monitored for tumor response and symptom relief, in addition to safety and tolerability.
- To estimate the duration of response to the proposed combined therapy.
- To measure the protein of regenerating liver-3 (PRL-3) level of expression in patients at time of relapse.
- To measure circulating biomarkers of response (soluble CD30 (sCD30), and thymus and activation-related chemokine (TARC)) in serum samples collected throughout treatment and inhibition of (pSTAT, pAKT) in peripheral blood mononucleated cells (PBMC).
- To measure cell-free messenger RNA (cfmRNA) in peripheral blood.
- To measure cell-free DNA in peripheral blood
|Condition or disease||Intervention/treatment||Phase|
|Hodgkin Lymphoma Refractory Hodgkin Lymphoma||Drug: Pentamidine||Phase 1|
The primary objective of this Phase I study is to determine the maximum tolerated dose (MTD) of Pentamidine. A two-stage continual reassessment method (CRM) will be employed to determine dose escalation levels and the maximum tolerated dose (MTD) of Pentamidine.
Specifically, a modified two-stage CRM will be employed with 2 patients per cohort at each dose level. The trial starts with an escalation design from the lowest dose (2 mg/kg) with a traditional 2+2 dose escalation method. After occurrence of the first DLT, dose assignment will be determined by the CRM (2 patients/per cohort) using empirical model with restrictions to avoid dose-skipping and escalation immediately after a toxicity outcome.
A maximum of 12 patients will be enrolled into the trial during the escalation phase. Once the MTD is reached, an additional 4 patients will be treated at this dose. Thus, 6 or more patients will be treated at the MTD.
The target DLT rate is 33% and the investigators choose to use 0.10, 0.20 and 0.33 as prior toxicity distribution. CRM simulations indicate optimal performance of this design with high dose recommendation probabilities (at least 48%) and more patients allocated to the correct dose
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Pentamidine in Combination With Salvage Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma|
|Actual Study Start Date :||December 19, 2018|
|Estimated Primary Completion Date :||July 2020|
|Estimated Study Completion Date :||July 2030|
Experimental: Pentamidine + ICE
Pentamidine, Ifosfamide, Carboplatin, and Etoposide (ICE) by IV Infusion.
Pentamidine will be administered as an IV infusion on treatment day 1-3 of a 21-day cycle 3 cycles using 2, 3, and 4 mg/kg dose escalation schedules. Non-investigational agents will be administered as follows: Ifosfamide 5000 mg/m2, Carboplatin 5 area under curve (AUC), and Etoposide 100 mg/mg2.
- Maximum tolerated dose (MTD) [ Time Frame: Up to 21 days ]Dose limiting toxicity (DLT) for hematological and non-hematological toxicities will be graded using National Cancer Institute (NCI) CTCAE Version 5.0
- Determine Efficacy: best overall response [ Time Frame: Up to 112 days ]Individual best overall response at 5 and 16 weeks from enrollment, patients will be categorized as either a responder (complete response, partial response) versus nonresponders (stable disease, progressive disease).
- Define the Duration of Response [ Time Frame: Up to 112 days ]Duration of response as defined starting from the first occurrence of response until disease progression or death.
- Identify Immunohistochemistry Biomarkers [ Time Frame: Up to 112 days ]Immunohistochemistry staining of paraffin fixed tissue sample and peripheral blood will be done to assess the ability of pentamidine to inhibit its pharmacological target through PRL-3 expression.
- Polymerase Chair Reaction (PCR) analysis of Biomarkers [ Time Frame: Up to 112 days ]Digital PCR analysis of paraffin fixed tissue sample and peripheral blood will be done to assess PRL-3 expression and compare to the immunohistochemistry staining to determine the ideal testing modality for PRL-3 in cHL.
- Identify Phosphorylation Biomarkers [ Time Frame: Up to 112 days ]Pentamidine concentration/protein phosphorylation will be measured in PBMC and plasma samples collected throughout treatment.
- Identify sCD30 and TARC Biomarkers [ Time Frame: Up to 112 days ]Biomarkers: ELISA testing will be used to assess levels of sCD30 and TARC in serum samples collected prior to initiation of therapy and subsequent cycles.
- Measure cfmRNA Biomarkers [ Time Frame: Up to 112 days ]Digital PCR analysis of the peripheral blood plasma will be used to measure cfmRNA during therapy
- Measure Circulating-free DNA (cfDNA) Biomarkers [ Time Frame: Up to 112 days ]digital PCR analysis of the peripheral blood plasma will be used to measure cfDNA during therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03730363
|Contact: Jeri Reynoldsfirstname.lastname@example.org|
|Contact: Heather Heathemail@example.com|
|United States, Kentucky|
|University of Kentucky Markey Cancer Center||Recruiting|
|Lexington, Kentucky, United States, 40536|
|Contact: Jeri Reynolds|
|Principal Investigator: Hayder Saeed, MD|
|Principal Investigator:||Hayder Saeed, MD||Lucille P. Markey Cancer Center at University of Kentucky|