Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Biomarker-Based Treatment of Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03013998
Recruitment Status : Recruiting
First Posted : January 9, 2017
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Beat AML, LLC

Brief Summary:
This screening and multi-sub-study Phase 1b/2 trial will establish a method for genomic screening followed by assigning and accruing simultaneously to a multi-study "Master Protocol (BAML-16-001-M1)." The specific subtype of acute myeloid leukemia will determine which sub-study, within this protocol, a participant will be assigned to evaluate investigational therapies or combinations with the ultimate goal of advancing new targeted therapies for approval. The study also includes a marker negative sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies.

Condition or disease Intervention/treatment Phase
Previously Untreated Acute Myeloid Leukemia Biological: Samalizumab (BAML-16-001-S1) Biological: BI 836858 (BAML-16-001-S2) Other: Laboratory Biomarker Analysis Drug: Daunorubicin (BAML-16-001-S1) Drug: Cytarabine (BAML-16-001-S1) Drug: Azacitidine (BAML-16-001-S2) Drug: AG-221 (BAML-16-001-S3) Drug: Azacitidine (BAML-16-001-S3) Drug: Entospletinib (BAML-16-001-S4) Drug: Azacitidine (BAML-16-001-S4) Drug: Entospletinib (BAML-16-001-S5) Drug: Decitabine (BAML-16-001-S5) Drug: Entospletinib (BAML-16-001-S6) Drug: Azacitidine (BAML-16-001-S6) Drug: Daunorubicin (BAML-16-001-S6) Drug: Cytarabine (BAML-16-001-S6) Drug: Pevonedistat (BAML-16-001-S9) Drug: Azacitidine (BAML-16-001-S9) Drug: AG-120 (BAML-16-001-S16) Drug: Azacitidine (BAML-16-001-S16) Drug: Gilteritinib (BAML-16-001-S8) Drug: Decitabine (BAML-16-001-S8) Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Master Protocol for Biomarker-Based Treatment of AML (The Beat AML Trial)
Study Start Date : November 2016
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: BAML-16-001-S1
This is an open-label Phase 1b/2 clinical study of Samalizumab given in addition to standard induction chemotherapy/consolidation, followed by Samalizumab maintenance, in newly diagnosed acute myeloid leukemia. Patients that are marker negative, as defined based on the Beat AML Master Protocol assignment or with CBF karyotype/interphase cytogenetics/molecular testing defined by presence of t(8;21)(q22;q22) or the molecular equivalent RUNX1/RUNX1T1 fusion transcript or inv(16)(p13q22) or t(16;16)(p13;q22) or the molecular equivalent CBFB/MYH11 fusion transcript based on the Beat AML will receive Samalizumab in combination with induction therapy followed by Samalizumab maintenance.
Biological: Samalizumab (BAML-16-001-S1)
300 mg/m2, IV, on days 1, 3, and 24; followed by 300 mg/m2, IV, every 21 days for 2 years in the absence of toxicity or disease progression. Dose may be de-escalated to 150 mg/m2 or escalated to 600 mg/m2 based on occurrence of dose-limiting toxicity.

Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: Daunorubicin (BAML-16-001-S1)
60 mg/m2, IV, on days 4, 5, and 6 of the induction cycle

Drug: Cytarabine (BAML-16-001-S1)
100 mg/m2, IV, on days 4 through 10 of the 24-day induction cycle; 1000 mg/m2, IV, on days 2, 4, and 6 of the consolidation cycle 1 and days 1, 3, and 5 of consolidation cycles 2 through 4

Experimental: BAML-16-001-S2
This is an open-label Phase 1b/2 clinical study of BI 836858 given in combination with azacitidine, followed by BI 836858 plus azacitidine maintenance, in newly diagnosed acute myeloid leukemia. The target population is assigned by the Beat AML Master Protocol (the "umbrella" study). Eligible patients will have previously untreated acute myeloid leukemia, age greater than or equal to 60, with any 1 of the following: mutated TET2, IDH1, IDH2, or WT1, or "marker negative" as defined by the overall Beat AML umbrella protocol.
Biological: BI 836858 (BAML-16-001-S2)
20 mg/m2, IV, on days 9, 16, and 23 of a 28-day cycle; followed 20 by mg/m2, IV, on days 1, 8, 15 and 22 of each 28-day cycle for 2 years in the absence of toxicity or disease progression (reduced to monthly administration in event of complete response or complete response with incomplete blood count recovery). Dose may be escalated to a maximum dose of 320 mg/m2 or de-escalated to 10 mg/m2 based on occurrence of dose-limiting toxicity.

Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: Azacitidine (BAML-16-001-S2)
75 mg/m2, IV, on days 1 through 7 of each 28-day cycle for 2 years in the absence of toxicity or disease progression

Experimental: BAML-16-001-S3
This is a phase 2 clinical trial to assess the feasibility and efficacy of a stepwise approach to the treatment of IDH2-mutant AML. On day 1 of the trial, all enrolled participants will be initiated on therapy with the IDH2 inhibitor AG-221 for IDH2 R140 and R172-mutant patients. The dosing will be based on phase 1 experience of AG-221, which has established 100 mg daily as a safe and tolerated dose, with preliminary suggestion of efficacy. These will be administered continuously in 28 day cycles. Hydroxyurea will be allowed for the purposes of cytoreduction.
Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: AG-221 (BAML-16-001-S3)
100 mg, oral, daily until time of intolerance or disease progression. Dose may be de-escalated to 50 mg based on occurrence of dose-limiting toxicity.
Other Name: Enasidenib

Drug: Azacitidine (BAML-16-001-S3)
75 mg/m2, IV or SC, on days 1 through 7 of each 28-day cycle starting with cycle 6 and ending after 12 cycles for patients not attaining complete remission or complete remission with incomplete blood count recovery after 5 cycles of monotherapy with AG-221

Experimental: BAML-16-001-S4
This is a 2 cohort phase 1b/2 clinical trial to assess the feasibility and efficacy of entospletinib (ENTO) stepwise approach to the treatment of patients with balanced translocations of MLL identified cytogenetically (Cohort 1) and patients with MLL-partial tandem duplications identified molecularly (Cohort 2). All enrolled participants will be initiated on monotherapy with ENTO 400 mg PO BID. This dose will be administered continuously in 28 day cycles.
Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: Entospletinib (BAML-16-001-S4)
200 mg, oral, twice daily for 5 years until time of intolerance or disease progression. Dose may be escalated to 400 mg.
Other Name: GS-9973, ENTO

Drug: Azacitidine (BAML-16-001-S4)
75 mg/m2, IV or SC, on days 1 through 7 of each 28-day cycle and continuing for 12 cycles. Treatment starts after 1 cycle of monotherapy with entospletinib for patients not attaining complete remission or complete remission with incomplete blood count recovery or after later cycles of monotherapy with entospletinib for patients with disease progression.

Experimental: BAML-16-001-S5
This is a phase 2 clinical trial to assess the feasibility and efficacy of a stepwise approach to the treatment of patients with TP53 mutations (identified molecularly) with/without complex karyotype (Cohort A) or complex karyotype (3 or greater metaphase abnormalities without TP53) (Cohort B). All enrolled participants will be initiated on entospletinib 400 mg orally twice daily. This dose will be administered continuously in 28 day cycles.
Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: Entospletinib (BAML-16-001-S5)
400 mg, oral, twice daily for 5 years until time of intolerance or disease progression. Dose may be de-escalated to 200 mg twice daily or 200 mg once daily based on occurrence of dose-limiting toxicity.
Other Name: GS-9973, ENTO

Drug: Decitabine (BAML-16-001-S5)
20 mg/m2, IV, on days 1 through 5 or 10 of each 28-day cycle and continuing for up to 11 cycles. Treatment starts after 1 cycle of monotherapy with entospletinib if subsequent induction cycles are necessary and continues for up to 2 total induction cycles including decitabine, with administration on days 1 through 10 of each 28-day cycle. During subsequent consolidation, decitabine is administered on days 1 through 5 of each 28-day cycle and continuing for up to 11 cycles. Duration may be reduced by up to 2 days based on occurrence of dose-limiting toxicity, and patients may switch to entospletinib monotherapy maintenance at any time if they develop toxicity or are unwilling to continue decitabine during consolidation therapy.

Experimental: BAML-16-001-S6
The study is an open-label phase 2 study of entospletinib in older AML patients with NPM1+/FLT3ITD- AML. It includes 2 Cohorts: patients 1) age <75 years; 2) have ECOG performance status of 0-1, and 3) are willing to receive 7 + 3 intensive chemotherapy (Cohort A); and patients who do not meet criteria for Cohort A (Cohort B). In Cohort A, entospletinib lead-in is administered on days 1-5 as a single agent (Cycle 0) and is then given daily with IV daunorubicin (days 1-3 for Cycle 1) and cytarabine (days 1-7 for Cycle 1). If a second induction is required, it is given with IV daunorubicin (days 1-2 for Cycle 2) and cytarabine (days 1-5 for Cycle 2). In Cohort B, for subjects receiving monotherapy, entospletinib is given daily for every 28 day cycle until the subject meets criteria for treatment discontinuation; for subjects receiving combination therapy, entospletinib is administered daily on days 1-28 as a single agent (Cycle 1) with azacitidine on days 1-7 of subsequent 28 day cycles
Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: Entospletinib (BAML-16-001-S6)
400 mg, oral, twice daily for 5 years until time of intolerance or disease progression.
Other Name: GS-9973, ENTO

Drug: Azacitidine (BAML-16-001-S6)
75 mg/m2, IV or SC, on days 1 through 7 of each 28-day cycle and continuing for 12 cycles. Treatment starts after 1 cycle of monotherapy with entospletinib for patients not attaining complete remission or complete remission with incomplete blood count recovery.

Drug: Daunorubicin (BAML-16-001-S6)
60 mg/m2, IV, on days 1-3 or 1-2 of each 28-day cycle for the first and second induction cycle, respectively

Drug: Cytarabine (BAML-16-001-S6)
100 mg/m2, IV, on days 1 through 7 or 1 through 5 of each 28-day cycle for the first and second induction cycle, respectively; 1000 mg/m2, IV, on days 1, 3, and 5 of each 28-day cycle for the consolidation cycles

Experimental: BAML-16-001-S9
This is an open-label phase 2 clinical trial of a stepwise approach to the treatment of patients with TP53 mutation AML. On day 1, all enrolled participants will be initiated on therapy with pevonedistat (20 mg/m2) day 1, 3 and 5 together with azacitidine (75 mg/m2 days 1-7 or day 1-5 then day 8, 9) every 28 days. During cycle 1, patients with rapidly progressive disease or severe organ dysfunction, not correctable by hydroxyurea cytoreduction will not be eligible to continue. Those patients who achieved a response, defined as complete response or complete response with incomplete blood count recovery, by the end of cycle 4 will continue on pevonedistat and azacitidine until disease progression, unacceptable toxicity, or 12 cycles of therapy. After 12 months of combined therapy, pevonedistat will be continued until progression of disease, unacceptable toxicity, or up to 2 years of total therapy.
Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: Pevonedistat (BAML-16-001-S9)
20 mg/m2, IV, on days 1, 3, and 5 of each 28-day cycle and continuing for 24 cycles in the absence of toxicity or disease progression
Other Name: TAK-924, MLN4924

Drug: Azacitidine (BAML-16-001-S9)
75 mg/m2, IV or SC, on days 1 through 7 or days 1 through 5 and then 8 through 9 (based on institutional guidelines) of each 28-day cycle and continuing for 12 cycles in the absence of toxicity or disease progression

Experimental: BAML-16-001-S16
This is an open-label phase 2 clinical study to assess the feasibility and efficacy of a combination based approach to the treatment of IDH1 mutant AML. On day 1 of the trial, all enrolled participants will be initiated on therapy with the IDH1 inhibitor AG-120 given daily together with azacitidine (days 1-5 and 8-9 or 7 consecutive days 1-7) in 28 day cycles for IDH1 mutant patients. Those patients who have achieved a response, defined as complete response or complete response with incomplete blood count recovery, by the end of cycle 6, will continue on combination therapy for a total of 12 cycles and then patients will go onto receive monotherapy with AG-120 until disease progression or unacceptable side effects that mandate discontinuation of therapy. Patients who cannot complete 12 cycles of azacitidine may proceed onto monotherapy with AG-120.
Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: AG-120 (BAML-16-001-S16)
500 mg, oral, daily until time of intolerance or disease progression. Dose may be de-escalated to 250 mg based on occurrence of dose-limiting toxicity.

Drug: Azacitidine (BAML-16-001-S16)
75 mg/m2, IV or SC, on days 1 through 7 or days 1 through 5 and then 8 through 9 (based on institutional guidelines) of each 28-day cycle and continuing for 12 cycles in the absence of toxicity or disease progression

Experimental: BAML-16-001-S8
This is an open-label Phase 2/1b clinical study of gilteritinib as a single agent stratified into 2 cohorts in phase 2 portion based upon dominant versus non-dominant FLT3 mutation status. Cohort 1, Dominant FLT3, will include patients with either FLT3-ITD with allelic ratio of ≥0.5 stratified based upon the prioritization schema of the master trial; FLT3-TKD with highest variant allele frequency among mutations studied for stratification; or FLT3-TKD with second highest variant allele frequency in setting of DNMT3A, TET2, ASXL1, BCORL1, JAK2, and SF3B1 or other spliceosome family member. Cohort 2, non-dominant FLT3, will include the remainder of patients with FLT3-ITD or FLT3-TKD stratified based upon the master umbrella study protocol. For the phase 1b portion, gilteritinib will be given in combination with decitabine for non-responding patients to test the efficacy of gilteritinib in combination with decitabine in elderly AML with FLT3 mutation.
Other: Laboratory Biomarker Analysis
Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Drug: Gilteritinib (BAML-16-001-S8)

120 mg, oral, daily, with treatment continuing based on bone marrow results at 28 and 56 days. Patients with partial response at 28 days continue treatment for an additional 28 days. Patients with complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) at 28 or 56 days continue treatment for 5 years until time of intolerance or disease progression. Patients with less than partial response at 28 days or partial response at 28 days followed by less than CR or CRi at 56 days proceed to combination treatment with decitabine or non-study alternative.

The combination dose is 80 mg, oral, daily, for 5 years until time of intolerance or disease progression (patients who do not achieve CR or CRi after 3 cycles will discontinue study treatment). The combination dose may be escalated to 120 mg daily or de-escalated to 80 mg daily given after decitabine rather than in combination with decitabine based on absence or occurrence of dose-limiting toxicity.


Drug: Decitabine (BAML-16-001-S8)
20 mg/m2, IV, on days 1 through 10 of each 28-day cycle and continuing for up to 3 cycles. Treatment starts after 1-2 cycles of monotherapy with gilteritinib if patients do not attain complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with monotherapy. Patients who do not achieve CR/CRi after 3 cycles of combination therapy will discontinue study treatment. If CR or CRi is obtained with combination therapy after 3 cycles, decitabine will be administered on days 1-5 of each subsequent 28-day cycle until progression, intolerance, or patient desire to discontinue therapy.




Primary Outcome Measures :
  1. Proportion of patients for whom molecular, immunophenotypic, and/or biochemical studies are completed in < 7 calendar days for assignment of treatment [ Time Frame: 7 days ]
    The feasibility of completing molecular, genetic, immunophenotypic, and biochemical testing for assignment of therapy will be assessed based on the proportion of patients for whom testing is completed within 7 days of the registration sample arriving at the laboratory

  2. Proportion of patients assigned to a novel therapeutic treatment group in 1 of several sub-studies in this Master Protocol, based on the result of the molecular, immunophenotypic, and/or biochemical studies [ Time Frame: 7 days ]
    The feasibility of assigning patients to a treatment group will be assessed based on the proportion who are eligible for screening in this study who are assigned to treatment either on this study or an industry study relevant to the specific marker group and not unassignable due to insufficient material, laboratory error, or any other factors

  3. Clinical response rate (rate of complete and partial responses) according to International Working Group criteria for treatment outcomes in therapeutic trials in acute myeloid leukemia [ Time Frame: Up to 5 years ]

Secondary Outcome Measures :
  1. Proportion of patients enrolled on this trial that ultimately will be assigned and go onto an assigned therapy [ Time Frame: 7 days ]
  2. Dynamic changes in clonal architecture over time in acute myeloid leukemia patients receiving targeted therapies [ Time Frame: time of diagnosis, remission (complete response or complete response with incomplete blood count recovery), 1 year of treatment, and relapse ]
  3. Relationships between baseline functional status and response rate or progression-free survival based on graphical comparison (eg, side-by-side boxplots or Kaplan-Meier plots) [ Time Frame: Up to 5 years ]
    Assessments of functional status will include Eastern Cooperative Oncology Group Performance Status. Assessment of clinical response will be made according to International Working Group criteria. Relationships will be explored graphically (eg, side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.



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.


Layout table for eligibility information
Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults, age 60 years or older at the time of diagnosis
  • Subjects or their legal representative must be able to understand and provide written informed consent
  • Cohort Inclusion Criteria - Group A: Subjects must have previously untreated acute myeloid leukemia (AML) according to the WHO classification with no prior treatment other than hydroxyurea. Prior therapy for myelodysplastic syndrome (MDS), myeloproliferative syndromes (MPD), or aplastic anemia is permitted but not with hypomethylating agents.
  • Cohort Inclusion Criteria - Group B: Subjects must have relapsed or refractory AML according to the WHO classification. For study purposes, refractory AML is defined as failure to ever achieve CR or recurrence of AML within 6 months of achieving CR; relapsed AML is defined as all others with disease after prior remission. (Group B is not currently recruiting.)

Exclusion Criteria:

  • Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study)
  • Acute promyelocytic leukemia
  • Symptomatic central nervous system (CNS) involvement by AML
  • Signs of leukostasis requiring urgent therapy
  • Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
  • Patients with psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up
  • Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial

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): NCT03013998


Contacts
Layout table for location contacts
Contact: Spencer Kalk 919-227-5843 spencer.kalk@incresearch.com

Locations
Layout table for location information
United States, Arizona
Mayo Clinic Arizona Recruiting
Phoenix, Arizona, United States, 85054
Principal Investigator: Lisa Sproat, MD         
United States, California
UCLA Ronald Reagan Medical Center Recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Gary Schiller, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Principal Investigator: Rebecca Olin, MD         
United States, Colorado
University of Colorado Recruiting
Denver, Colorado, United States, 80203
Principal Investigator: Dan Pollyea, MD         
United States, Florida
Mayo Clinic Florida Recruiting
Jacksonville, Florida, United States, 32224
Principal Investigator: James Foran, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30308
Principal Investigator: William Blum, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Wendy Stock, MD         
United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Maria Baer, MD         
United States, Minnesota
Mayo Clinic Minnesota Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Mark R Litzow, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Principal Investigator: Eytan M Stein, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Principal Investigator: John C Byrd, MD         
Principal Investigator: Alice Mims, MD         
Principal Investigator: Alison R Walker, MD, MPH         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Principal Investigator: Uma Borate, MD         
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Principal Investigator: Prapti Patel, MD         
United States, Utah
Huntsman Cancer Institute, University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Principal Investigator: Michael Deininger, MD, PhD         
Sponsors and Collaborators
Beat AML, LLC
Investigators
Layout table for investigator information
Principal Investigator: John C Byrd, MD Beat AML

Additional Information:
Layout table for additonal information
Responsible Party: Beat AML, LLC
ClinicalTrials.gov Identifier: NCT03013998     History of Changes
Other Study ID Numbers: BAML-16-001
First Posted: January 9, 2017    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms by Histologic Type
Neoplasms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Azacitidine
Decitabine
Daunorubicin
Ivosidenib
Pevonedistat
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors