Pentamidine + Salvage Chemo for Relapsed/Refractory Classical Hodgkin Lymphoma

Hodgkin Lymphoma Clinical Trial

Official title: A Phase I Study of Pentamidine in Combination With Salvage Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma

Status Completed

Clinical Trial Summary

Primary Objective:

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).

Secondary Objective:

• 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).

Exploratory Objective:

• To measure cell-free messenger RNA (cfmRNA) in peripheral blood.

• To measure cell-free DNA in peripheral blood

Clinical Trial Description

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 ;

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma
• Refractory Hodgkin Lymphoma

• NCT number: NCT03730363
• Study type: Interventional
• Source: University of Kentucky
• Status: Completed
• Phase: Phase 1
• Start date: December 19, 2018
• Completion date: May 23, 2019