Advanced Chronic Myelogenous Leukemia (CML) - Follow On: Study of BMS-354825 in Subjects With CML

Leukemia, Lymphoblastic, Acute, Philadelphia-Positive Clinical Trial

Official title:

A Randomized Two-Arm, Multicenter, Open-Label Phase III Study of BMS-354825 Administered Orally at a Dose of 70 mg Twice Daily or 140 mg Once Daily in Subjects With Chronic Myeloid Leukemia in Accelerated Phase or in Myeloid or Lymphoid Blast Phase or With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Who Are Resistant or Intolerant to Imatinib Mesylate (Gleevec)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00123487
• Other study ID #: CA180-035
• Status: Completed
• Phase: Phase 3
• First received: July 21, 2005
• Last updated: October 30, 2014
• Start date: June 2005
• Est. completion date: June 2013

Study information

• Verified date: October 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a phase III study of BMS-354825 in subjects with chronic myelogenous leukemia in accelerated phase, or in myeloid or lymphoid blast phase or with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia who are resistant or intolerant to imatinib mesylate (Gleevec).

Other known NCT identifiers

• NCT00331396

Recruitment information / eligibility

• Status: Completed
• Enrollment: 638
• Est. completion date: June 2013
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• Patients with Philadelphia-Positive (Ph+) (or BCR/ABL+) accelerated phase chronic myeloid leukemia, Ph+ (or BCR/ABL+) blast phase chronic myeloid leukemia, or Ph+ (or BCR/ABL+) acute lymphoblastic leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate

• Men and women, 18 years of age or older

• Adequate hepatic function

• Adequate renal function

• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized

• Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2

Exclusion Criteria:

• Women who are pregnant or breastfeeding

• A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy

• Uncontrolled or significant cardiovascular disease

• Medications that increase bleeding risk

• Medications that change heart rhythms

• Dementia or altered mental status that would prohibit the understanding or rendering of informed consent

• History of significant bleeding disorder unrelated to CML

• Concurrent incurable malignancy other than CML

• Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy

• Prior therapy with BMS-35425

• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Myeloid Leukemia, Chronic, Accelerated Phase
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• dasatinib
Tablets, Oral, 70 mg BID, indefinitely, survival study
• dasatinib
Tablets, Oral, 140 mg QD, indefinitely, survival study

Locations

Country	Name	City	State
Argentina	Local Institution	Capital Federal	Buenos Aires
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Parkville	Victoria
Australia	Local Institution	Perth	Western Australia
Australia	Local Institution	South Brisbane	Queensland
Australia	Local Institution	St Leonards	New South Wales
Austria	Local Institution	Wien
Belgium	Local Institution	B-leuven
Belgium	Local Institution	Brugge
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Charleroi
Belgium	Local Institution	Yvoir
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Morumbi	Sao Paulo
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Vancouver	British Columbia
Czech Republic	Local Institution	Brno
Czech Republic	Local Institution	Prague 2
Denmark	Local Institution	Aarhus C
Denmark	Local Institution	Herlev
Denmark	Local Institution	Odense C
Finland	Local Institution	Helsinki
France	Local Institution	Caen Cedex
France	Local Institution	Creteil Cedex
France	Local Institution	Grenoble Cedex 9
France	Local Institution	Lille Cedex
France	Local Institution	Lyon Cedex
France	Local Institution	Marseille Cedex 9
France	Local Institution	Nantes
France	Local Institution	Paris Cedex 10
France	Local Institution	Pessac
France	Local Institution	Poitiers Cedex
France	Local Institution	Strasbourg Cedex
Germany	Local Institution	Dresden
Germany	Local Institution	Frankfurt
Germany	Local Institution	Hamburg
Germany	Local Institution	Leipzig
Germany	Local Institution	Mainz
Germany	Local Institution	Mannheim
Greece	Local Institution	Athens
Hungary	Local Institution	Budapest
Ireland	Local Institution	Dublin
Israel	Local Institution	Ramat-gan
Italy	Local Institution	Bari
Italy	Local Institution	Bologna
Italy	Local Institution	Monza
Italy	Local Institution	Napoli
Italy	Local Institution	Orbassano (to)
Italy	Local Institution	Roma
Korea, Republic of	Local Institution	Jeollanam-do
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Netherlands	Local Institution	Rotterdam
Norway	Local Institution	Trondheim
Peru	Local Institution	Jesus Maria	Lima
Peru	Local Institution	Lima
Philippines	Local Institution	Quezon City
Poland	Local Institution	Gdansk
Poland	Local Institution	Katowice
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Lublin
Poland	Local Institution	Warsaw
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	St.petersburg
Singapore	Local Institution	Singapore
South Africa	Local Institution	Bloemfontein	Free State
South Africa	Local Institution	Groenkloof	Gauteng
South Africa	Local Institution	Observatory	Western Cape
South Africa	Local Institution	Parktown	Gauteng
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Valencia
Sweden	Local Institution	Lund
Sweden	Local Institution	Stockholm
Sweden	Local Institution	Umea
Sweden	Local Institution	Uppsala
Switzerland	Local Institution	Basel
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taoyuan
Thailand	Local Institution	Bangkok
United Kingdom	Local Institution	Edinburgh
United Kingdom	Local Institution	Glasgow	Scotland
United Kingdom	Local Institution	Liverpool
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	Newcastle	Tyne And Wear
United States	Emory University School Of Medicine	Atlanta	Georgia
United States	University Of Maryland	Baltimore	Maryland
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	Dana Faber Cancer Institute	Boston	Massachusetts
United States	The University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	The University Of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Karmanos Cancer Center	Detroit	Michigan
United States	The Cancer Center At Hackensack University Medical Center	Hackensack	New Jersey
United States	The University Of Texas Md Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University Of Kentucky	Lexington	Kentucky
United States	Loma Linda University Cancer Center	Loma Linda	California
United States	Ucla Dept. Of Medicine	Los Angeles	California
United States	University Of Miami	Miami	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	The Cancer Institute Of New Jersey	New Brunswick	New Jersey
United States	New York Presbyterian Hospital	New York	New York
United States	Devetten, Marcel	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania
United States	Oregon Health & Sci Univ	Portland	Oregon
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Washington Cancer Institute At Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Norway,  Peru,  Philippines,  Poland,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

References & Publications (1)

Chu SC, Tang JL, Li CC. Dasatinib in chronic myelogenous leukemia. N Engl J Med. 2006 Sep 7;355(10):1062-3; author reply 1063-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population	MaHR defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) = upper limit of normal (ULN); absolute neutrophil count (ANC) = 1,000/mm^3; platelets = 100,000/mm^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts = 5%; <5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percentage: number of participants with MaHR/number of randomized participants.	Randomization up to 6 months	No
Secondary	Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population	A MaHR was defined as a participant having either CHR or NEL. CHR was defined as: WBC = ULN; ANC = 1,000/mm^3; - platelets = 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts = 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (both lower limits had to be satisfied): platelets = 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percent: number of participants with MaHR /number of participants randomized.	Randomization up to 2 years	No
Secondary	Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population	MaHR was defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) = upper limit of normal (ULN); absolute neutrophil count (ANC) = 1,000/mm^3; platelets = 100,000/mm^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts = 5%; <5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one parameter of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule.. Percentage: participants with MaHR/randomized participants.	Randomization up to 2 years	No
Secondary	Median Time to Major Hematologic Response (MaHR) - Randomized Population	A participants' time to MaHR was defined as the time from the first dosing date until criteria are first met for CHR or NEL, whichever occurred first. Non-responders were censored at the maximum of the date of last hematologic or cytogenetic assessment. Median time was measured in months.	Day 1 up to 6 months (time of primary endpoint), 2 years	No
Secondary	Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study	MaHR was defined by either CHR or no evidence of leukemia NEL. CHR was defined as: WBC = ULN; ANC = 1,000/mm^3; - platelets = 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts = 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. Median duration was measured in months.	Day 1 up to 5 years	No
Secondary	Percent of Participants With Overall Hematologic Response - Randomized Population	Overall Hematologic Response (OHR) was defined as CHR, NEL or minor hematologic response (MiHR). CHR was defined as: WBC = ULN; ANC = 1,000/mm^3; - platelets = 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts = 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. MiHR defined as: < 15% blasts in BM and in PB; < 30% blasts + promyelocytes in BM and PB; < 20% basophils in PB; No extra-medullary disease other than spleen and liver. Percentage: participants with OHR/ randomized participants.	Randomization up to 6 Months, 2 Years	No
Secondary	Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population	Type of hematologic response: CHR defined as: WBC = ULN; ANC = 1,000/mm^3; - platelets = 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts = 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets = 20,000/mm^3 and <100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. Minor Hematologic Response (MiHR): <15% blasts in BM and in PB; < 30% blasts + promyelocytes in BM and PB; < 20% basophils in PB; No extra-medullary disease other than spleen and liver. Major hematologic response (MaHR ) was CHR or NEL. Overall hematologic response was CHR or NEL or MiHR.	Randomization up to 6 months, 2 years	No
Secondary	Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population	Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM; Major cytogenetic response (MCyR) was defined as CCyR or PCyR. Percentage: number of participants with MCyR and denominator is number of randomized participants.	Randomization up to 6 Months, 2 Years	No
Secondary	Number of Participants With Best Cytogenic Response (CyR) - Randomized Population	Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM.	Randomization up to 6 Months, 2 Years	No
Secondary	Median Progression Free Survival (PFS) - Randomized Population	PFS was defined as: Time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. Median duration was measured in months.	Randomization up to 5 Years	No
Secondary	Median Overall Survival (OS) - Randomized Population	OS was defined as time from randomization until date of death. Participants who had not died or who were lost to follow-up were censored on the last date on which the participant was known to be alive. Median duration was measured in months.	Randomization up to 5 Years	No
Secondary	Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population	PFS was defined as time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. OS was defined as time from randomization until date of death. Participants who had not died or were lost to follow-up were censored on the last date they were known to be alive. Median duration was measured in months.	24 months, 36 months, 48 months, 60 months	No
Secondary	Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants	With protocol Amendment 6, the duration of the study was extended for 2 additional years (7 years total) for participants who continued to have clinical benefit and no feasible alternate access to dasatinib. However, after Year 5 the requirement to follow participants for survival and to collect other efficacy data was removed from the protocol for the remainder of the study. Only AEs and SAEs were collected up to Year 7. On-study AEs and SAEs were graded by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The investigator AE terms were coded and grouped by preferred term and system organ class using the Medical Dictionary for Regulatory Activities (MedDRA), version 16.0.	Day 1 to Year 7	Yes
Secondary	Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants	Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) version 3.0. CTC Grade 3 and 4 criteria are defined as follows: White blood cells (WBC): Grade (Gr) 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. Absolute neutrophil count (ANC): Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Baseline was laboratory value obtained within 2 weeks prior to randomization.	Baseline to Year 2	Yes
Secondary	Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations	Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) Version 3.0. Grade 4 hematology evaluations used to determine myelosuppression included: WBC: <1.0*10^9/L. ANC: <0.5*10^9/L. Platelet count <25.0 to 10^9/L.	Day 1 up to Year 7	Yes
Secondary	Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants	Laboratory abnormalities were graded according to the NCI CTC version 3.0. Grade 3 and 4 criteria were defined as follows: Upper limit of normal (ULN). Alanine transaminase (ALT) Grade (Gr) 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Aspartate aminotransferase (AST) Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. Serum creatinine (H) Gr 3: >3.0 to 6.0*ULN; Gr 4: >6.0*ULN. Calcium (L) Gr3: 6.0-7.0; Gr 4: <6.0 mg/dL; Phosphorus (L): Gr 3: <2.0 - 1.0 mg/dL , Gr 4: <1.0 mg/dL. Non-hematologic laboratory results were not collected beyond Year 2. Baseline values were obtained within 2 weeks prior to randomization.	Baseline to Year 2	Yes
Secondary	Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants	A12-lead electrocardiogram (ECG) was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Days 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. The QT interval corrected with Fridericia formula is presented with categories of changes from baseline (BL) in milliseconds (msec).	Baseline to Year 2	Yes
Secondary	Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants	A12-lead ECG was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Day 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. QT Interval corrected with Fridericia formula was measured in msec.	Baseline up to Year 2	Yes

External Links

•   BMS clinical trial educational resource
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•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form