Advanced B-cell Lymphoid MalignanciesEarly Phase 1NCT01888952
Phase 0/1 Biomarker and Pharmacodynamic Study of Roflumilast in Patients With Advanced B-Cell Hematologic Malignancies (CTRC# 13-0013)
A Early Phase 1 study testing Prednisone and Roflumilast in people with Advanced B-cell Lymphoid Malignancies, run by Anand B. Karnad at 1 site in United States.
Trial summary
This is a Phase 0/1 open-label, non-randomized, biomarker and pharmacodynamic study in patients with advanced B-cell lymphoid malignancies, including B-cell chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), acute lymphocytic leukemia (ALL), multiple myeloma (MM), Waldenström's macroglobulinemia… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Advanced B-cell Lymphoid Malignancies
- What is being tested?
- Prednisone and Roflumilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Jan 2015
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent.
- Men and women > 18 years of age
- Diagnosed with relapsed or refractory (per investigator assessment) B-cell hematologic malignancy, including CLL, SLL, ALL, MM, WM, mantle cell lymphoma, follicular lymphoma, or DLBCL that has progressed or recurred following prior therapy. Patients must have failed, refused, be ineligible, or not otherwise appropriate for any potential standard curative treatment. In addition, patients must be refractory to or intolerant of established therapy known to provide clinical benefit for their condition. The original diagnostic biopsy and/or other diagnostic data (e.g., cell marker data) will suffice.
- Has failed ≥ 1 previous treatment for their malignancy, and has relapsed or refractory disease following most recent prior treatment.
- ECOG performance status of ≤ 2 and a life expectancy of at least 3 months.
- Ability to swallow oral tablets without difficulty.
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- All subjects with preserved reproductive potential must agree to practice abstinence or employ contraceptive measures for the duration of treatment and for 4 weeks following final dosing.
- All male subjects are considered to have reproductive potential.
- Female subjects of reproductive potential are those who: 1) are not at least 50 years old and have no menses for 24 consecutive months; or 2) have not been rendered surgically sterile (having undergone hysterectomy and/or bilateral salpingo-oophorectomy).
- Female subjects of reproductive potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin ([hCG]) within 7 days of first day of drug dosing.
- Has recovered from adverse, toxic effects of prior therapies to ≤ Grade 1(NCI-CTCAE v4) except for alopecia and peripheral neuropathy. This requirement will be subordinate to specific clinical and laboratory criteria that are otherwise specifically addressed in these inclusion/exclusion criteria. Peripheral neuropathy must have recovered to ≤ Grade 2 except for patients with WM, who may enroll with Grade 3 peripheral neuropathy if due to the underlying WM.
- Meet the following clinical laboratory requirements:
- All patients, except ALL:
- Creatinine clearance by Cockcroft-Gault formula of ≥30 ml/min
- Total bilirubin ≤ 1.5 × ULN (unless indirect bilirubin is elevated due to Gilbert's syndrome or hemolysis)
- Aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) ≤ 3 × ULN
- Platelet count ≥ 50,000/uL, patients may be transfused to this value.
- Absolute neutrophil count (ANC) ≥ 1000/uL, with or without chronic granulocyte growth factor support
- Hemoglobin ≥8 g/dL, patients may be transfused to this value
- For patients with ALL and CLL:
- The hematological criteria do not apply.
Who cannot join
- Prior allogeneic bone marrow transplant within 6 months of screening date.
- Prior autologous stem cell transplant within 3 months of screening date.
- Active central nervous system (CNS) involvement by lymphoma, including untreated symptomatic epidural disease.
- Patients with autoimmune hemolytic anemia or immune thrombocytopenia requiring on-going active immunotherapy at study entry other than systemic corticosteroids less than or equal to prednisone equivalent 20 mg/day.
- Allergy or intolerance to roflumilast.
- Immunotherapy, chemotherapy, radiotherapy or investigational therapy within 3 weeks (within 4 weeks for monoclonal antibodies; within 6 weeks for nitrosoureas; within 12 weeks for iodine-131 tositumomab and ibritumomab tiuxetan) prior to study drug dosing.
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- Active uncontrolled infection.
- Is receiving concurrent high doses of systemic corticosteroids. High dose is considered as >20 mg of dexamethasone a day (or equivalent) for >7 consecutive days.
- Uncontrolled illness including but not limited to: symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV heart failure), unstable angina pectoris, uncontrolled cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements.
- History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within 6 months prior to study drug dosing.
- History of another currently active cancer or any other cancer < 2 years prior to study drug dosing, except for adequately treated basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other adequately treated in situ carcinoma.
- Patients with a history of major surgery within 3 weeks or minor surgery within one week of roflumilast administration. Major surgery includes, for example, any open or laparoscopic entry into a body cavity, or operative repair of fracture; minor surgery includes, for example, open surgical biopsy of palpable/superficial lymph node, or placement of vascular access device.
- Other medical or psychiatric illness or organ dysfunction, which in the opinion of the investigator, would either compromise the subject's safety or interfere with the evaluation of the safety of the study agent.
- Corrected QT interval (QTc) prolongation (defined as a QTc >450 msec for males and >470 msec for females [Fridericia's correction]) or other clinically significant ECG abnormalities as assessed by the investigator.
- Patients known to be HIV-positive must not have multi-drug resistant HIV infection, CD4 counts < 150/mcl or other concurrent AIDS-defining conditions.
- Patients positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C-virus ribonucleic acid (HCV RNA), unless both AST and ALT≤1.25 x ULN and no known history of chronic active hepatitis.
- Patients with moderate to severe liver impairment (Child-Pugh B or C)
- Women who are pregnant or breastfeeding.
- Patients with a history of depression or other psychiatric illness
- Patients who are taking strong cytochrome P450 enzyme inducers and inhibitors.
Trial locations and contacts
1 site in 1 country.
About this study
This is a Phase 0/1 open-label, non-randomized, biomarker and pharmacodynamic study in patients with advanced B-cell lymphoid malignancies, including B-cell chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), acute lymphocytic leukemia (ALL), multiple myeloma (MM), Waldenström's macroglobulinemia (WM), mantle cell lymphoma, follicular lymphoma, or diffuse large B-cell lymphoma (DLBCL) who have failed at least one prior therapy and for whom no standard curative therapy exists. Patients with advanced stage disease are those whose disease is resistant or refractory to standard chemotherapy or biological therapies.
Read the detailed description
This pilot study will evaluate whether the administration of roflumilast inhibits the activity of PDE4 and results in the modulation of AKT/mTOR pathways in patients with B-cell hematologic malignancies. Peripheral blood samples will be collected for the purpose of determining the pharmacodynamics of roflumilast on PDE4 activity and on biomarkers as related to GC resistance. Samples are obtained at baseline prior to starting study treatment, on Day 8 before the administration of the Day 8 study drugs (prednisone and roflumilast), and on Day 15. If a bone marrow biopsy is also performed prior to study treatment or at any time during treatment, a sample will be sent for analysis. Normal PBMC (and bone marrow when it is obtained) will be examined for changes in key targets related to the inhibition of PDE4 and potential reversal of glucocorticoid resistance. Biomarker blood samples will be analyzed in order to characterize the pharmacodynamics of roflumilast alone and in combination with prednisone on PDE4 activity and on biomarkers, such as phospho-AKT, phosphorylation levels of mTOR targets.
- Conditions
- Advanced B-cell Lymphoid Malignancies
- Being tested
- Prednisone, Roflumilast
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoneDrug
Also called Deltasone
Patients may receive additional courses of treatment with prednisone (and roflumilast) at the discretion of the investigator if they did not experience unacceptable toxicity and have stable disease or objectively responding disease.
RoflumilastDrug
Also called Daliresp
Patients may receive additional courses of treatment with roflumilast (and prednisone) at the discretion of the investigator if they did not experience unacceptable toxicity, and have stable disease or objectively responding disease.
| Study group | Role | What they receive |
|---|---|---|
| Roflumilast and Prednisone | Experimental | Roflumilast 500 mcg will be administered orally daily for 21 consecutive days (a 21-day cycle).
In Cycle 1, prednisone 60 mg/m2 up to a maximum of 100 mg oral (PO) daily will be taken on Days 8 through 14 at the same time as roflumilast.
In Cycle 2 and subsequent cycles, prednisone 60 mg/m2 PO up to a maximum of 100 mg daily will be taken on Days 1 through 7 at the same time as roflumilast. Receives: Drug: Prednisone; Drug: Roflumilast |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Adverse Events.
Adverse events were listed using CTCAE Version 4.03 (Common Terminology Criteria for Adverse Events) toxicity grade.
Measured: Average of 21 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2013 (estimated)
- Study startJul 2013
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced B-cell Lymphoid MalignanciesStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anand B. Karnad
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Anand B. Karnad, The University of Texas Health Science Center at San Antonio
- Investigators
- Anand Karnad, MD, Principal investigator, CTRC @ UTHSCSARicardo Aguiar, MD PhD, Principal investigator, CTRC @ UTHSCSA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01888952
- Sponsor's protocol ID
- CTRC 13-0013
- Other IDs
- HSC20130307H
- Status last verified
- Jan 2017
- First submitted
- 8 May 2013
- Last updated
- 27 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 0/1 Biomarker and Pharmacodynamic Study of Roflumilast in Patients With Advanced B-Cell Hematologic Malignancies (CTRC# 13-0013)
- ClinicalTrials.gov ID
- NCT01888952
- Acronym / sponsor ID
- CTRC 13-0013
- Conditions
- Advanced B-cell Lymphoid Malignancies
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Anand B. KarnadUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 28 Jun 2013 (estimated)
- Results
- Posted 27 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 0/1 open-label, non-randomized, biomarker and pharmacodynamic study in patients with advanced B-cell lymphoid malignancies, including B-cell chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), acute lymphocytic leukemia (ALL), multiple myeloma (MM), Waldenström's macroglobulinemia (WM), mantle cell lymphoma, follicular lymphoma, or diffuse large B-cell lymphoma (DLBCL) who have failed at least one prior therapy and for whom no standard curative therapy exists. Patients with advanced stage disease are those whose disease is resistant or refractory to standard chemotherapy or biological therapies.
Detailed description
This pilot study will evaluate whether the administration of roflumilast inhibits the activity of PDE4 and results in the modulation of AKT/mTOR pathways in patients with B-cell hematologic malignancies. Peripheral blood samples will be collected for the purpose of determining the pharmacodynamics of roflumilast on PDE4 activity and on biomarkers as related to GC resistance. Samples are obtained at baseline prior to starting study treatment, on Day 8 before the administration of the Day 8 study drugs (prednisone and roflumilast), and on Day 15. If a bone marrow biopsy is also performed prior to study treatment or at any time during treatment, a sample will be sent for analysis. Normal PBMC (and bone marrow when it is obtained) will be examined for changes in key targets related to the inhibition of PDE4 and potential reversal of glucocorticoid resistance. Biomarker blood samples will be analyzed in order to characterize the pharmacodynamics of roflumilast alone and in combination with prednisone on PDE4 activity and on biomarkers, such as phospho-AKT, phosphorylation levels of mTOR targets.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Roflumilast and Prednisone | Experimental | Drug: Prednisone, Drug: RoflumilastRoflumilast 500 mcg will be administered orally daily for 21 consecutive days (a 21-day cycle). In Cycle 1, prednisone 60 mg/m2 up to a maximum of 100 mg oral (PO) daily will be taken on Days 8 through 14 at the same time as roflumilast. In Cycle 2 and subsequent cycles, prednisone 60 mg/m2 PO up to a maximum of 100 mg daily will be taken on Days 1 through 7 at the same time as roflumilast. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Signed informed consent.
- Men and women > 18 years of age
- Diagnosed with relapsed or refractory (per investigator assessment) B-cell hematologic malignancy, including CLL, SLL, ALL, MM, WM, mantle cell lymphoma, follicular lymphoma, or DLBCL that has progressed or recurred following prior therapy. Patients must have failed, refused, be ineligible, or not otherwise appropriate for any potential standard curative treatment. In addition, patients must be refractory to or intolerant of established therapy known to provide clinical benefit for their condition. The original diagnostic biopsy and/or other diagnostic data (e.g., cell marker data) will suffice.
- Has failed ≥ 1 previous treatment for their malignancy, and has relapsed or refractory disease following most recent prior treatment.
- ECOG performance status of ≤ 2 and a life expectancy of at least 3 months.
Key exclusion criteria (20 listed)
- Prior allogeneic bone marrow transplant within 6 months of screening date.
- Prior autologous stem cell transplant within 3 months of screening date.
- Active central nervous system (CNS) involvement by lymphoma, including untreated symptomatic epidural disease.
- Patients with autoimmune hemolytic anemia or immune thrombocytopenia requiring on-going active immunotherapy at study entry other than systemic corticosteroids less than or equal to prednisone equivalent 20 mg/day.
- Allergy or intolerance to roflumilast.
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 |
|---|---|---|
| PrednisoneAlso: DeltasonePatients may receive additional courses of treatment with prednisone (and roflumilast) at the discretion of the investigator if they did not experience unacceptable toxicity and have stable disease or objectively responding disease. | Drug | Roflumilast and Prednisone |
| RoflumilastAlso: DalirespPatients may receive additional courses of treatment with roflumilast (and prednisone) at the discretion of the investigator if they did not experience unacceptable toxicity, and have stable disease or objectively responding disease. | Drug | Roflumilast and Prednisone |
Primary outcome
Total Number of Adverse Events.
Time frame: Average of 21 days.
Adverse events were listed using CTCAE Version 4.03 (Common Terminology Criteria for Adverse Events) toxicity grade.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Anand Karnad, MD principal investigator
CTRC @ UTHSCSA
Ricardo Aguiar, MD PhD principal investigator
CTRC @ UTHSCSA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Prednisone and Roflumilast in people with Advanced B-cell Lymphoid Malignancies, run by Anand B. Karnad 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 21 inclusion and 20 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 27 Feb 2017. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Total Number of Adverse Events. (time frame: Average of 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 27 Feb 2017.