Hodgkin LymphomaPhase 1NCT03730363
Pentamidine + Salvage Chemo for Relapsed/Refractory Classical Hodgkin Lymphoma
A Phase 1 study testing Pentamidine in people with Hodgkin Lymphoma and Refractory Hodgkin Lymphoma, run by Reinhold Munker at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin Lymphoma, Refractory Hodgkin Lymphoma
- What is being tested?
- Pentamidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2018to 23 May 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
About this study
Official title: A Phase I Study of Pentamidine in Combination With Salvage Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma
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).
Read more
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
Read the 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
- Being tested
- Pentamidine
- Keywords
- Pentamidine, Salvage Chemotherapy
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PentamidineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Pentamidine + ICE | Experimental | Pentamidine, Ifosfamide, Carboplatin, and Etoposide (ICE) by IV Infusion. Receives: Drug: Pentamidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 21 days
Secondary outcomes (6)
Determine Efficacy: best overall response
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).
Measured: Up to 112 days
Define the Duration of Response
Duration of response as defined starting from the first occurrence of response until disease progression or death.
Measured: Up to 112 days
Identify Immunohistochemistry Biomarkers
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.
Measured: Up to 112 days
Polymerase Chair Reaction (PCR) analysis of Biomarkers
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.
Measured: Up to 112 days
Identify Phosphorylation Biomarkers
Pentamidine concentration/protein phosphorylation will be measured in PBMC and plasma samples collected throughout treatment.
Measured: Up to 112 days
Identify sCD30 and TARC Biomarkers
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.
Measured: Up to 112 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2018
- Study start19 Dec 2018
- Primary completion23 May 2019
- Study completion23 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Reinhold Munker
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Reinhold Munker, University of Kentucky
- Investigators
- Hayder Saeed, MD, Principal investigator, Lucille P. Markey Cancer Center at University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03730363
- Sponsor's protocol ID
- MCC-18-HEM-13
- Status last verified
- Jul 2021
- First submitted
- 26 Oct 2018
- Last updated
- 7 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Pentamidine in Combination With Salvage Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT03730363
- Acronym / sponsor ID
- MCC-18-HEM-13
- Conditions
- Hodgkin Lymphoma, Refractory Hodgkin Lymphoma
- Keywords
- Pentamidine, Salvage Chemotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Reinhold MunkerUniversity, hospital or other
- Study start
- 19 Dec 2018 (actual)
- Primary completion
- 23 May 2019 (actual)
- Study completion
- 23 May 2019 (actual)
- First posted
- 5 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pentamidine + ICE | Experimental | Drug: PentamidinePentamidine, Ifosfamide, Carboplatin, and Etoposide (ICE) by IV Infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PentamidinePentamidine 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. | Drug | Pentamidine + ICE |
Primary outcome
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
6 secondary outcomes
Determine Efficacy: best overall response
Time frame: Up to 112 days
Define the Duration of Response
Time frame: Up to 112 days
Identify Immunohistochemistry Biomarkers
Time frame: Up to 112 days
Polymerase Chair Reaction (PCR) analysis of Biomarkers
Time frame: Up to 112 days
Identify Phosphorylation Biomarkers
Time frame: Up to 112 days
Identify sCD30 and TARC Biomarkers
Time frame: Up to 112 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hayder Saeed, MD principal investigator
Lucille P. Markey Cancer Center at University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pentamidine in people with Hodgkin Lymphoma and Refractory Hodgkin Lymphoma, run by Reinhold Munker at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: Up to 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2021.