Pentamidine + Salvage Chemo for Relapsed/Refractory Classical Hodgkin Lymphoma

NCT03730363 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MCC-18-HEM-13
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Hodgkin Lymphoma; Refractory Hodgkin Lymphoma

Keywords

Pentamidine; Salvage Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Dose limiting toxicity (DLT) for hematological and non-hematological toxicities will be graded using National Cancer Institute (NCI) CTCAE Version 5.0

  Up to 21 days

Secondary Outcomes (6)

• Determine Efficacy: best overall response

  Up to 112 days

• Define the Duration of Response

  Up to 112 days

• Identify Immunohistochemistry Biomarkers

  Up to 112 days

• Polymerase Chair Reaction (PCR) analysis of Biomarkers

  Up to 112 days

• Identify Phosphorylation Biomarkers

  Up to 112 days

Other Outcomes (2)

• Measure cfmRNA Biomarkers

  Up to 112 days

• Measure Circulating-free DNA (cfDNA) Biomarkers

  Up to 112 days

Study Arms (1)

Pentamidine + ICE

EXPERIMENTAL

Pentamidine, Ifosfamide, Carboplatin, and Etoposide (ICE) by IV Infusion.

Drug: Pentamidine

Interventions

Pentamidine DRUG

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.

Pentamidine + ICE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years old or older
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Subjects with histologically confirmed relapse or refractory cHL who had received a front-line anthracycline-containing regimen.
• Subjects must have at least one measurable lesion \>1.5cm as defined by the lymphoma response criteria.
• Subjects must have recovered from their last prior chemotherapy; if they have received an investigational agent, at least 5 half-lives must have expired to assure clearance of prior therapy.
• Prior radiation should have been completed at least 4 weeks prior to study Day 1.
• Toxicities related to prior therapy must have returned to Grade 1 or less except for alopecia. Peripheral neuropathy must be grade 2 or less.
• Adequate bone marrow function defined as: 1) Absolute neutrophil count ≥ 1000/µl and 2) Platelet count ≥ 50,000/µl
• Adequate organ function: 1) Creatinine Clearance (CrCl) \>60 mL/min and 2) Aspartate Aminotransferase (AST) ≤ 3 upper limit normal (ULN), and Alanine Aminotransferase (ALT) ≤3 ULN, and Bilirubin ≤ 1.5 ULN (Unless they have Gillbert's disease)
• Ability to comply with the treatment, evaluations and required study follow-up.

You may not qualify if:

• Subjects with central nervous system involvement.
• Subjects with concomitant second malignancy (except adequately treated non-melanoma skin cancer, ductal carcinoma in-situ, superficial bladder cancer, prostate cancer or in situ cervical cancer) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated.
• A serious uncontrolled medical disorder or active infection which impairs the ability of the subject to receive protocol therapy or whose control is jeopardized by the complication of this therapy.
• Prior organ allograft or allogeneic bone marrow transplantation.
• Positive for HIV (1/2) or known acquired immunodeficiency syndrome.
• Positive for hepatitis B Surface Ag, or antibody to hepatitis B core ag, or hepatitis C antibody or hepatitis C RNA in serum.
• Ejection fraction less than 45% in subjects with prior anthracycline therapy (measurement of ejection fraction is mandatory).
• Corrected QT interval (QTc) prolongation of more than 500.
• Women of reproductive age who are unwilling or unable to use an acceptable method to minimize the risk of pregnancy for the entire study period and for at least 18 weeks after the last dose of pentamidine.
• Women who are pregnant or breast-feeding.
• Women with a positive pregnancy test (serum assay) on enrollment or prior to pentamidine administration.
• Sexually active men not using birth control if their partners are women of reproductive age.
• Prisoner or subjects who are involuntarily incarcerated.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pentamidine and/or ifosfamide, carboplatin and etoposide.
• No investigational or commercial agents or therapies other than those specified by the protocol may be administered with the intent to treat the patient's malignancy.

Sponsors & Collaborators

• Reinhold Munker: lead

Study Sites (1)

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Pentamidine

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamidines; Amidines; Organic Chemicals

Study Officials

• Hayder Saeed, MD

  Lucille P. Markey Cancer Center at University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 26, 2018
• First Posted: November 5, 2018
• Study Start: December 19, 2018
• Primary Completion: May 23, 2019
• Study Completion: May 23, 2019
• Last Updated: July 7, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)