Phase 0/1 Biomarker and Pharmacodynamic Study of Roflumilast in Patients With Advanced B-Cell Hematologic Malignancies (CTRC# 13-0013)

NCT01888952 | Completed Early Phase 1 Results DMC

• 2 other identifiers: CTRC 13-0013HSC20130307H
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Advanced B-cell Lymphoid Malignancies

Outcome Measures

Primary Outcomes (1)

• Total Number of Adverse Events.

  Adverse events were listed using CTCAE Version 4.03 (Common Terminology Criteria for Adverse Events) toxicity grade.

  Average of 21 days.

Study Arms (1)

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.

Drug: Prednisone; Drug: Roflumilast

Interventions

Prednisone DRUG

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.

Also known as: Deltasone

Roflumilast and Prednisone

Roflumilast DRUG

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.

Also known as: Daliresp

Roflumilast and Prednisone

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Anand B. Karnad: lead

Study Sites (1)

Ctrc @ Uthscsa

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

Prednisone; Roflumilast

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Anand Karnad, MD
• Organization: CTRC@UTHSCSA

karnad@uthscsa.edu

210-450-1000

Study Officials

• Anand Karnad, MD

  CTRC @ UTHSCSA

  PRINCIPAL INVESTIGATOR

• Ricardo Aguiar, MD PhD

  CTRC @ UTHSCSA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early 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: May 8, 2013
• First Posted: June 28, 2013
• Study Start: July 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: February 27, 2017
• Results First Posted: February 27, 2017

Record last verified: 2017-01

Locations

US (1)