NCT03730363

Pentamidine + Salvage Chemo for Relapsed/Refractory Classical Hodgkin Lymphoma

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Reinhold Munker · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Detailed 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

Conditions

• Hodgkin Lymphoma
• Refractory Hodgkin Lymphoma

Interventions

Type	Name	Description
DRUG	Pentamidine	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.

Timeline

• Start date: 2018-12-19
• Primary completion: 2019-05-23
• Completion: 2019-05-23
• First posted: 2018-11-05
• Last updated: 2021-07-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study