Rituximab and Dexamethasone Followed by Mycophenolate Mofetil or Placebo in Patients With Immune Thrombocytopenia

NCT02649504 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: 1501015858
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigators will attempt to further increase the cure rate of ITP with medical therapy by providing maintenance therapy with Mycophenolate mofetil (MMF) to persistent/chronic ITP patients after treating them with induction therapy combining rituximab and dexamethasone. The investigators will randomly assign patients to MMF versus placebo in order to demonstrate safety (e.g., for infectious risk) and efficacy (platelet counts stably \>50x109/L more than 1 year off therapy).

Conditions

Immune Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• Number of patients with a platelet count greater or equal to 50,000 for 5 of 6 platelet counts in the second half of second year (month 19 to month 24) with no rescue therapy

  2 years

Study Arms (2)

R+3D, MMF

ACTIVE COMPARATOR

Rituximab will be given at the standard dose of 375mg/m2 on days 1, 8, 15, 22 of the study. Dexamethasone will be given at dose 40 mg/day on days 1-4, 15-18, and 29-32 (+/- 3 days) of the study. Mycophenolate mofetil (MMF) will be given starting on day 33, 500 mg twice daily for the first week and then escalation to 1000 mg twice daily for 24 weeks.

Drug: Rituximab; Drug: Dexamethasone; Drug: Mycophenolate mofetil

R+3D, Placebo

PLACEBO COMPARATOR

Rituximab will be given at the standard dose of 375mg/m2 on days 1, 8, 15, 22 of the study. Dexamethasone will be given at dose 40 mg/day on days 1-4, 15-18, and 29-32 (+/- 3 days) of the study. Placebo will be given starting on day 33, 500 mg twice daily for the first week and then escalation to 1000 mg twice daily for 24 weeks.

Drug: Rituximab; Drug: Dexamethasone; Drug: Placebo

Interventions

Rituximab DRUG

Rituximab will be given at the standard dose of 375mg/m2 on days 1, 8, 15, 22 of the study

Also known as: anti- cluster of differentiation antigen 20 antibody

R+3D, MMF; R+3D, Placebo

Dexamethasone DRUG

Dexamethasone will be given at dose 40 mg/day on days 1-4, 15-18, and 29-32 (+/- 3 days) of the study.

Also known as: Decadron, Dexasone, Diodex, Hexadrol, Maxidex

R+3D, MMF; R+3D, Placebo

Mycophenolate mofetil DRUG

Patients allocated to the active drug arm will be given Mycophenolate mofetil starting on day 33, 500 mg twice daily for the first week and then escalation to 1000 mg twice daily for 24 weeks.

Also known as: Cellcept

R+3D, MMF

Placebo DRUG

Patients allocated to the placebo arm will be given placebo starting on day 33, 500 mg twice daily for the first week and then escalation to 1000 mg twice daily for 24 weeks.

Also known as: inactive drug, fake pill

R+3D, Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female, greater than 18 years old
• Signed written informed consent obtained prior to study entry
• Immune Thrombocytopenia according to the American Society of Hematology guidelines, with other potential causes of thrombocytopenia excluded, platelets less than 30 x 109/L at study entry
• Have adequate renal and hepatic function (creatinine and bilirubin less than 2 x Upper Limit of Normal (ULN), aspartate aminotransferase and alanine aminotransferase less than 3 x ULN)
• No significant cytopenias (hemoglobin greater than10 g/dL without ongoing transfusional support, absolute neutrophil count greater than 1.0 x109/L at study entry).
• If on corticosteroids, receiving less than or equal to 20 mg/day prednisone (or equivalent) with no change of dose for at least 2 weeks prior to study entry. No more than two 4-day courses of Dexamethasone prior to study entry. If on danazol, no change of dose for at least 2 weeks prior to study entry. (Thrombopoietin receptor agonist treatment will be allowed until the end of 8th week on study if started prior to study entry)
• No treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study
• No prior treatment with anti-B-lymphocyte antigen cluster of differentiation antigen 20 monoclonal antibody at a total dose greater than 375mg/m2
• Screen for Hepatitis B and be negative for Hepatitis B surface antigen
• Human Immunodeficiency Virus negative
• No history of active hepatitis C infection or a past history hepatitis C (confirmed by negative anti- Hepatitis C Virus Antibody)
• No past history of tuberculosis
• No chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, or chronic chest infection with bronchiectasis
• No current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease meeting laboratory threshold limits per investigator discretion)
• No significant concurrent, uncontrolled medical condition including but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease, which in the opinion of the investigator may represent a risk for the patient. Have no past or current malignancy for 3 years (excluding nonmelanoma skin cancers, e.g., basal cell carcinoma (BCC) and carcinoma in situ of the cervix)

You may not qualify if:

• Pregnant or lactating women
• Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study or until at least 6 months after treatment. Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy will be excluded from study. Adequate contraception is defined as intrauterine device, tubal sterilization, patient's partner had a vasectomy or total abstinence. Other contraceptive methods include hormonal contraceptive pills. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy will be excluded from the study as well.
• Immunosuppressive agents or ITP treatments or other experimental treatments for ITP within 2 weeks. Intravenous Immunoglobulin, anti-Rh(D) prior to first day of rituximab treatment
• Splenectomy or any other surgery within 4 weeks
• Red blood cell transfusion or hospitalization for bleeding within 4 weeks
• Concomitant anticoagulation therapy (warfarin, enoxaparin, dabigatran, rivaroxaban, apixaban, fondaparinux) or any platelet aggregation inhibitors including aspirin and clopidogrel (until platelets stable greater than 100x109/L)
• New York Heart Classification III or IV heart disease. Other severe cardiovascular or cardiopulmonary disease, including chronic obstructive pulmonary disease
• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Related Publications (5)

• Bussel JB, Lee CS, Seery C, Imahiyerobo AA, Thompson MV, Catellier D, Turenne IG, Patel VL, Basciano PA, Elstrom RL, Ghanima W. Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration. Haematologica. 2014 Jul;99(7):1264-71. doi: 10.3324/haematol.2013.103291. Epub 2014 Apr 18.

  PMID: 24747949 BACKGROUND

• Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001 Aug 15;98(4):952-7. doi: 10.1182/blood.v98.4.952.

  PMID: 11493438 BACKGROUND

• Stasi R, Stipa E, Forte V, Meo P, Amadori S. Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura. Blood. 2002 May 15;99(10):3872-3. doi: 10.1182/blood-2002-02-0392. No abstract available.

  PMID: 12014370 BACKGROUND

• Patel VL, Mahevas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, Kanter J, Neufeld E, Taube T, Ramenghi U, Shenoy S, Ward MJ, Mihatov N, Patel VL, Bierling P, Lesser M, Cooper N, Bussel JB. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood. 2012 Jun 21;119(25):5989-95. doi: 10.1182/blood-2011-11-393975. Epub 2012 May 7.

  PMID: 22566601 BACKGROUND

• Zaja F, Baccarani M, Mazza P, Bocchia M, Gugliotta L, Zaccaria A, Vianelli N, Defina M, Tieghi A, Amadori S, Campagna S, Ferrara F, Angelucci E, Usala E, Cantoni S, Visani G, Fornaro A, Rizzi R, De Stefano V, Casulli F, Battista ML, Isola M, Soldano F, Gamba E, Fanin R. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood. 2010 Apr 8;115(14):2755-62. doi: 10.1182/blood-2009-07-229815. Epub 2010 Feb 3.

  PMID: 20130241 BACKGROUND

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Rituximab; Dexamethasone; Calcium Dobesilate; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• James B. Bussel, M.D

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: January 7, 2016
• Study Start: December 1, 2016
• Primary Completion: December 1, 2016
• Last Updated: August 14, 2018

Record last verified: 2018-08