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Trial record 3 of 11 for:    STELLAR | Recruiting, Not yet recruiting Studies

A Trial of CHOP-R Therapy, With or Without Acalabrutinib, in Patients With Newly Diagnosed Richter's Syndrome (STELLAR)

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ClinicalTrials.gov Identifier: NCT03899337
Recruitment Status : Not yet recruiting
First Posted : April 2, 2019
Last Update Posted : April 2, 2019
Sponsor:
Collaborators:
Bloodwise
Acerta Pharma, LLC
Information provided by (Responsible Party):
University of Birmingham

Brief Summary:

The STELLAR trial will assess the effect of acalabrutinib taken in combination with CHOP-R compared to taking CHOP-R alone in patients with newly diagnosed Richter's Syndrome (RS). It will also be a platform to test other new drugs that show potential for treating RS. Chronic lymphocytic Leukaemia (CLL) is the most common blood cancer in adults, usually in their 70s or older. In a few patients, CLL can transform from a slow-growing cancer into an aggressive lymphoma called Richter's Syndrome. RS is very difficult to treat and patients have a short life-expectancy - usually a few months after diagnosis. Treatment for Richter's Syndrome in the UK is CHOP (four chemotherapy drugs) plus rituximab ('R' - an antibody treatment). The CHOP-R treatment is given as a standard of care for RS but has limited benefit - it is often temporary to extend life. Richter's Syndrome returns in most patients who then die from this disease. The STELLAR trial will investigate if a new drug called acalabrutinib, which is effective used by itself in patients with relapsed CLL and also some with Richter's Syndrome, will improve outcomes for newly diagnosed patients with RS. Acalabrutinib blocks a protein in CLL which can stop the cancer growing.

Participants who have Richter's Syndrome and are suitable for CHOP-R will be recruited by specialised hospitals across the UK. People with another cancer, heart problems, or recent stroke cannot take part. Participants will have a lymph node biopsy, 3-4 bone marrow biopsies, blood samples, and PET-CT and CT scans. CHOP-R is given in a hospital every three weeks up to 6 times. All participants will receive CHOP-R; half will also receive acalabrutinib. When treatment with CHOP-R ends the patients who had acalabrutinib can continue to take it; patients who had CHOP-R alone may have acalabrutinib if their Richter's Syndrome returns after CHOP-R.


Condition or disease Intervention/treatment Phase
Richter Syndrome Drug: Acalabrutinib Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisolone Drug: Rituximab Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Randomised Study of CHOP-R in Combination With Acalabrutinib Compared to CHOP-R in Patients With Newly Diagnosed Richter's Syndrome and a Platform for Initial Investigations Into Activity of Novel Treatments in Relapsed/Refractory and Newly Diagnosed Richter's Syndrome.
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Active Comparator: Standard of Care Arm (CHOP-R)

Arm in the randomised trial. CHOP-R chemoimmunotherapy will continue for up to 6 cycles (each cycle is 21 days), and will be given according to the following schedule:

Rituximab, 375 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Cyclophosphamide, 750 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Doxorubicin, 50 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Vincristine, 1.4 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Prednisolone, 40 mg/m2, PO, OD, 6 cycles, days of cycle: 1-5

Drug: Cyclophosphamide
750mg/m^2, IV bolus

Drug: Doxorubicin
50mg/m^2, IV bolus

Drug: Vincristine
1.4mg/m^2, IV infusion

Drug: Prednisolone
40mg/m^2, PO, OD
Other Name: Pevanti

Drug: Rituximab
375mg/m^2, IV infusion
Other Name: Mabthera

Experimental: Experimental Arm (CHOP-R + Acalabrutinib)

Arm in the randomised trial. CHOP-R chemoimmunotherapy will continue for up to 6 cycles (each cycle is 21 days), and will be given according to the following schedule:

Rituximab, 375 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Cyclophosphamide, 750 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Doxorubicin, 50 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Vincristine, 1.4 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Prednisolone, 40 mg/m2, PO, OD, 6 cycles, days of cycle: 1-5

Acalabrutinib 100 mg, PO, BD will be taken on days 6-21, of each cycle - up to cycle 6. Acalabrutinib treatment will be continuous thereafter until disease progression toxicity, patient choice or death.

Drug: Acalabrutinib
100mg capsule, PO, BD

Drug: Cyclophosphamide
750mg/m^2, IV bolus

Drug: Doxorubicin
50mg/m^2, IV bolus

Drug: Vincristine
1.4mg/m^2, IV infusion

Drug: Prednisolone
40mg/m^2, PO, OD
Other Name: Pevanti

Drug: Rituximab
375mg/m^2, IV infusion
Other Name: Mabthera

Experimental: Cohort 1 - Acalabrutinib Monotherapy - Platform Trial
Registration arm in platform study. Patients registered to Cohort 1 will receive 100 mg acalabrutinib monotherapy, twice daily, continuously from day 1 until disease progression, toxicity, patient choice or death.
Drug: Acalabrutinib
100mg capsule, PO, BD

Experimental: Cohort 2 - CHOP-R + Acalabrutinib - Platform Trial

Registration arm in platform study. CHOP-R chemoimmunotherapy will continue for up to 6 cycles (each cycle is 21 days), and will be given according to the following schedule:

Rituximab, 375 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Cyclophosphamide, 750 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Doxorubicin, 50 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Vincristine, 1.4 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Prednisolone, 40 mg/m2, PO, OD, 6 cycles, days of cycle: 1-5

Acalabrutinib 100 mg, PO, BD will be taken on days 6-21, of each cycle - up to cycle 6. Acalabrutinib treatment will be continuous thereafter until disease progression toxicity, patient choice or death.

Drug: Acalabrutinib
100mg capsule, PO, BD

Drug: Cyclophosphamide
750mg/m^2, IV bolus

Drug: Doxorubicin
50mg/m^2, IV bolus

Drug: Vincristine
1.4mg/m^2, IV infusion

Drug: Prednisolone
40mg/m^2, PO, OD
Other Name: Pevanti

Drug: Rituximab
375mg/m^2, IV infusion
Other Name: Mabthera




Primary Outcome Measures :
  1. Randomised Component - Progression free survival (PFS) [ Time Frame: Time from randomisation to the date of progression or death from any cause, whichever came first, assessed up to 24 months.. ]
    Progression free survival (PFS) defined as the time from randomisation to the date of progression or death from any cause. Progression will be defined by the modified Cheson criteria (Appendix 1). Patients who are alive and progression free at the time of analysis will be censored at date last seen. Any participants who withdraw or are lost to follow-up will also be censored at date last seen.

  2. Registration Arm - Cohort 1 - Overall Response [ Time Frame: Response assessed at 24 weeks of treatment ]
    Overall response after 24 weeks of treatment based on the modified Cheson criteria (Appendix 1). Complete response (CR) and partial response (PR) are considered to be positive responses for assessment of this outcome. Participants who withdraw prior to the 6 month assessment or do not have the 6 month assessment will be considered non responders.

  3. Registration Arm - Cohort 2 - Overall Response [ Time Frame: Response assessed after 6 cycles of treatment. Each cycle is 21 days. ]
    Overall response after 6 cycles of treatment, defined by the modified Cheson criteria (Appendix 1). CR and PR are considered to be positive responses for assessment of this outcome. Participants who withdraw prior to the post-cycle-6 assessment or do not have the post-cycle-6 assessment will be considered non-responders.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Time from trial entry to the date of death from any cause, whichever came first, assessed up to 24 months. ]

    Defined as time from date of randomisation (for randomised trial) or registration (to the relevant cohort for single-arm cohorts) to date of death from any cause.

    Participants who are alive at the time of analysis will be censored at date last seen.


  2. Overall Response after 6 cycles [ Time Frame: Response assessed after 6 cycles of treatment. Each cycle is 21 days. ]
    Overall response (randomised component only) after cycle 6, defined by the modified Cheson criteria (Appendix 1). CR and PR are considered to be positive responses for assessment of this outcome. Participants who withdraw prior to the post-cycle-6 assessment or do not have the post-cycle-6 assessment will be considered non-responders.

  3. Overall Response after 12 weeks [ Time Frame: Response assessed after 12 weeks of treatment ]
    Overall response (cohorts 1 only) after 12 weeks, defined by the modified Cheson criteria (Appendix 1). CR and PR are considered to be positive responses for assessment of this outcome. Participants who withdraw prior to the 12-week assessment or do not have the 12- week assessment will be considered non-responders.

  4. Progression Free Survival [ Time Frame: Time from date of registration to date of progression or death from any cause, whichever came first, assessed up to 24 months. ]
    PFS (single-arm cohorts only) defined as the time from date of registration to date of progression or death from any cause. Progression will be defined by the modified Cheson criteria (Appendix 1). Participants who are alive and progression free at the time of analysis will be censored at date last seen. Any patients who withdraw or are lost to follow-up will also be censored at date last seen.

  5. Quality of Life Questionnaire Outcomes [ Time Frame: Analysed at the end of cycles 4 (week 12) and 6 (week 24) ]
    QoL, (assessed using ECOG performance status [Appendix 7]), and the CLL17 and NHLHG29 questionnaires (Appendix 2)) at the end of cycles 4 and 6 for participants receiving CHOP-R as part of their treatment (randomised cohorts and Cohort 2), and at 12 and 24 weeks for participants receiving acalabrutinib monotherapy (Cohort 1).

  6. Exhibited Toxicity [ Time Frame: Measured from start of treatment until 28 days after last dose ]
    Toxicity defined as the number of participants who experience one or more adverse event grade 3 or higher or serious adverse event of any grade.

  7. Proportion of patients proceeding to allogeneic or autologous stem cell transplantation [ Time Frame: Confirmation of partial or complete remission, assessed at the following time points: Randomised Trial/ Platform Study - Cohort 2: Post Cycle 4, Post Cycle 6 (where each cycle is 21 days); Platform Study - Cohort 1: Week 12, Week 24. ]
    Measured as proportion of patients proceeding to transplant on each treatment arm, at confirmation of partial or complete remission



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Entry criteria for randomised trial component (standard of care and experimental arms):

Inclusion criteria for the randomised trial component:

  • Suitable for anthracycline-containing chemo-immunotherapy.
  • Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS.
  • ECOG performance status of 0, 1, 2 or 3.
  • Age 16 years and over.
  • Signed written informed consent prior to performing any study-specific procedures.

Exclusion criteria for the randomised trial component:

  • Prior therapy with CHOP or any anthracycline containing treatment at any time prior to randomisation. (Please note that pre-treatment with prednisolone up to 2mg/kg is allowed for up to 14 days prior to the start of treatment).
  • Ibrutinib-exposed CLL patients who have been newly diagnosed with RS within four weeks of their last dose of ibrutinib. (Ibrutinib-exposed CLL patients who discontinue ibrutinib due to toxicity or progressive CLL and later (more than four weeks) develop RS are not excluded from the randomised trial component).
  • Previous acalabrutinib exposure. (Prior exposure to other Bruton tyrosine kinase (BTK), phosphoinositide-3-kinase (PI3K), or BCL-2 inhibitors is permitted, with the exception of patients who have progressed on ibrutinib - see exclusion criterion above).
  • Known central nervous system (CNS) involvement of CLL or DLBCL.
  • Any other active malignancy that requires active treatment, with the exception of basal cell carcinoma, in-situ cervical cancer, and non-invasive squamous cell carcinoma of the skin.
  • Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active hepatitis
  • Positive serology for Hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg). In addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HBV deoxyribonucleic acid (DNA) test will be performed and if positive the patient will be excluded.
  • Known human immunodeficiency virus (HIV) positive.
  • Patients with active bleeding or history of bleeding diathesis (e.g. haemophilia, von Willebrand disease).
  • Patients receiving therapeutic anticoagulation with warfarin or equivalent (e.g. phenprocoumon).
  • Uncorrected prolonged prothrombin time (PT) or an activated partial thromboplastin time (APTT) > 2 x the upper limit of normal (ULN).
  • Major surgery within 30 days prior to randomisation and/or inadequate recovery (at Investigators discretion) from any prior major surgery, toxicity or complications.
  • Patients with malabsorption syndrome or medical conditions significantly affecting gastrointestinal function.
  • Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and unstable arrhythmias requiring therapy, with the exception of extra systoles or minor conduction abnormalities. Stable and controlled atrial fibrillation is not an exclusion.
  • Significant concurrent, uncontrolled severe medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
  • History of significant cerebrovascular disease in the 6 months prior to randomisation, including intracranial haemorrhage.
  • Known or suspected hypersensitivity to components of the investigational products
  • Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to proposed start of treatment unless discussed and approved by the Chief Investigator or Clinical Coordinator via the Trials Office.
  • Current participation in any other interventional clinical study.
  • Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
  • Breast feeding women or women with a positive pregnancy test at screening.
  • Women of childbearing potential and men not willing to use highly effective contraception during study and for 12 months after last dose of study therapy. Highly effective contraception is defined as abstinence, hormonal birth control, intrauterine devices, vasectomy/surgical sterilisation.

Entry criteria for single-arm relapsed Cohort 1:

Inclusion criteria for Cohort 1 (progressive RS following chemo-immunotherapy):

  • Patients with relapsed/refractory RS who received anthracycline based chemotherapy with anti-CD20 monoclonal antibody If fewer than the expected number of patients from the randomised component enter into Cohort 1, patients from outside STELLAR with relapsed/refractory RS following chemo-immunotherapy (anthracycline based chemotherapy with anti-CD20 monoclonal antibody) will be able to join this cohort if they meet the eligibility criteria. The Trials Office will alert sites by email if any slots are released for patients outside of STELLAR, these must be booked with the Trials Office prior to registration.
  • ECOG performance status of 0, 1, 2 or 3.
  • Age 16 years and over.
  • Signed written informed consent prior to performing any study-specific procedures.

Exclusion criteria for Cohort 1 (progressive RS following chemo-immunotherapy):

  • Previous acalabrutinib exposure. (Prior exposure to other Bruton tyrosine kinase (BTK), phosphoinositide-3-kinase (PI3K), or BCL-2 inhibitors is permitted).
  • Known central nervous system (CNS) involvement of CLL or DLBCL.
  • Any other active malignancy that requires active treatment, with the exception of basal cell carcinoma, in-situ cervical cancer, and non-invasive squamous cell carcinoma of the skin.
  • Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active hepatitis
  • Positive serology for Hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg). In addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HBV deoxyribonucleic acid (DNA) test will be performed and if positive the patient will be excluded.
  • Known human immunodeficiency virus (HIV) positive.
  • Patients with active bleeding or history of bleeding diathesis (e.g. haemophilia, von Willebrand disease).
  • Patients receiving therapeutic anticoagulation with warfarin or equivalent (e.g. phenprocoumon).
  • Uncorrected prolonged prothrombin time (PT) or an activated partial thromboplastin time (APTT) > 2 x the upper limit of normal (ULN).
  • Major surgery within 30 days prior to registration and/or inadequate recovery (at Investigators discretion) from any prior major surgery, toxicity or complications.
  • Patients with malabsorption syndrome or medical conditions significantly affecting gastrointestinal function.
  • Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and unstable arrhythmias requiring therapy, with the exception of extra systoles or minor conduction abnormalities. Stable and controlled atrial fibrillation is not an exclusion.
  • Significant concurrent, uncontrolled severe medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
  • History of significant cerebrovascular disease in the 6 months prior to registration, including intracranial haemorrhage.
  • Known or suspected hypersensitivity to components of the investigational products
  • Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to proposed start of treatment unless discussed and approved by the Chief Investigator or Clinical Coordinator via the Trials Office.
  • Current participation in any other interventional clinical study.
  • Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
  • Breast feeding women or women with a positive pregnancy test at screening.
  • Women of childbearing potential and men not willing to use highly effective contraception during study and for 12 months after last dose of study therapy. Highly effective contraception is defined as abstinence, hormonal birth control, intrauterine devices, vasectomy/surgical sterilisation.

Entry criteria for single arm Cohort 2

Inclusion criteria for Cohort 2 (anthracycline-naïve RS patients, diagnosed while on ibrutinib):

  • Ibrutinib-exposed CLL patients who have developed biopsy-proven DLBCL-type RS within four weeks of last dose of ibrutinib.
  • No previous anthracycline treatment and suitable for anthracycline-containing chemo-immunotherapy.
  • Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS.
  • ECOG performance status of 0, 1, 2 or 3.
  • Age 16 years and over.
  • Signed written informed consent prior to performing any study-specific procedures.

Exclusion criteria for Cohort 2 (anthracycline-naïve RS patients, diagnosed while on ibrutinib):

  • Prior therapy with CHOP or any anthracycline containing treatment at any time prior to registration. (Please note that pre-treatment with prednisolone up to 2mg/kg is allowed for up to 14 days prior to the start of treatment).
  • Previous acalabrutinib exposure. (Prior exposure to other Bruton tyrosine kinase (BTK), phosphoinositide-3-kinase (PI3K), or BCL-2 inhibitors is permitted)
  • Known central nervous system (CNS) involvement of CLL or DLBCL.
  • Any other active malignancy that requires active treatment, with the exception of basal cell carcinoma, in-situ cervical cancer, and non-invasive squamous cell carcinoma of the skin.
  • Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active hepatitis
  • Positive serology for Hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg). In addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HBV deoxyribonucleic acid (DNA) test will be performed and if positive the patient will be excluded.
  • Known human immunodeficiency virus (HIV) positive.
  • Patients with active bleeding or history of bleeding diathesis (e.g. haemophilia, von Willebrand disease).
  • Patients receiving therapeutic anticoagulation with warfarin or equivalent (e.g. phenprocoumon).
  • Uncorrected prolonged prothrombin time (PT) or an activated partial thromboplastin time (APTT) > 2 x the upper limit of normal (ULN).
  • Major surgery within 30 days prior to registration and/or inadequate recovery (at Investigators discretion) from any prior major surgery, toxicity or complications.
  • Patients with malabsorption syndrome or medical conditions significantly affecting gastrointestinal function.
  • Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and unstable arrhythmias requiring therapy, with the exception of extra systoles or minor conduction abnormalities. Stable and controlled atrial fibrillation is not an exclusion.
  • Significant concurrent, uncontrolled severe medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
  • History of significant cerebrovascular disease in the 6 months prior to registration, including intracranial haemorrhage.
  • Known or suspected hypersensitivity to components of the investigational products
  • Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to proposed start of treatment unless discussed and approved by the Chief Investigator or Clinical Coordinator via the Trials Office.
  • Current participation in any other interventional clinical study.
  • Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
  • Breast feeding women or women with a positive pregnancy test at screening.
  • Women of childbearing potential and men not willing to use highly effective contraception during study and for 12 months after last dose of study therapy. Highly effective contraception is defined as abstinence, hormonal birth control, intrauterine devices, vasectomy/surgical sterilisation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03899337


Contacts
Layout table for location contacts
Contact: Sophie Cramp, MSc +44 (0)121 371 7867 STELLAR@trials.bham.ac.uk
Contact: Francesca Yates, PhD +44 (0)121 371 7867 STELLAR@trials.bham.ac.uk

Sponsors and Collaborators
University of Birmingham
Bloodwise
Acerta Pharma, LLC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Birmingham
ClinicalTrials.gov Identifier: NCT03899337     History of Changes
Other Study ID Numbers: RG_17-194
First Posted: April 2, 2019    Key Record Dates
Last Update Posted: April 2, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by University of Birmingham:
Chronic Lymphocytic Leukaemia
Richter's Transformation
Richter's Syndrome
CHOP-R
Acalabrutinib
Diffuse Large B Cell Lymphoma
non-Hodgkin Lymphoma
Additional relevant MeSH terms:
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Syndrome
Disease
Pathologic Processes
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Cyclophosphamide
Rituximab
Doxorubicin
Liposomal doxorubicin
Vincristine
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic