MDACC Study Summary 2008-0241

Study Summary
No. 2008-0241:.......Advanced Cancers; Leukemia......Srdan Verstovsek......Leukemia

Study Summary Title



Study Summary Number:	2008-0241

Study Title:	A Phase 2, open label, dose regimen ranging clinical study to determine the safety and efficacy of INCB018424 in patients with advanced polycythemia vera or essential thrombocythemia refractory to hydroxyurea

Physician

New Patient Referral



Name:	Srdan Verstovsek	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Leukemia	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-745-3429 Contact us about clinical trials

General Information



Disease Group:	Advanced Cancers Leukemia	Supported By:	Incyte Corporation

Phase of Study:	Phase II	Return Visit:	n/a

Treatment Agents:	INCB018424	Home Care:	n/a

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	n/a


Description/ Intervention:	The goal of this clinical research study is to learn if INCB018424 can help to control PV and ET. The safety of this drug will also be studied.

Study Objectives / Outcomes

Primary Endpoints for PV Patients

1. Complete, partial and overall (CR + PR) response rates will be assessed for all PV patients treated with INCB018424. Response will be assessed at individual time points, but to be a confirmed response, it must be sustained for at least 2 months. The following criteria will be used:

Complete Clinical Response (requires all of the following):

o Hematocrit (Hct) lower than 45% in men and 42% in women
o No phlebotomy procedures for 1 month
o Absence of palpable splenomegaly
o White blood cell count < 10 x 109/L with normal differential and platelet count < 400 x 109/L
o Absence of sustained leucopenia or thrombocytopenia (> 2 weeks) based on institutional normal ranges
o Absence of systemic symptoms attributable to PV (pruritus, night sweats, bone pain, fever, weight loss)
Partial Clinical Response (requires all of the following):
o Hct < 45% in men and < 42% in women
o Reduction in phlebotomy requirements by 50% compared to six months prior to treatment initiation
o 50% reduction in palpable splenomegaly
2. Safety and tolerability as assessed by monitoring frequency, duration, and severity of adverse events graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3, and the results of laboratory, electrocardiogram findings, vital sign measurements and physical examinations.

Primary Endpoints for ET Patients

1. Complete, partial and overall (CR+PR) response rates will be assessed for all ET patients treated with INCB018424. Response will be assessed at individual time points but to be a confirmed response it must be sustained for at least 2 months. The following criteria will be used:

Complete Clinical Response (requires all of the following):

o Platelet count < 400 x 109/L
o White blood cell count < 10 x 109/L with normal differential and Hct ≤ upper limit of normal (ULN)
o Absence of sustained (> 2 weeks) anemia or leucopenia based on institutional normal ranges
o Absence of systemic symptoms attributable to ET (pruritus, bone pain, weakness, night sweats, paresthesias)
o Absence of palpable splenomegaly

Partial Clinical Response (requires all of the following):

o Platelet count < 400 x 109/L
o 50% reduction in palpable splenomegaly
2. Safety and tolerability as assessed by monitoring frequency, duration, and severity of adverse events graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3, and the results of laboratory, electrocardiogram findings, vital sign measurements and physical examinations.

Secondary endpoints include measurements of Pharmakodynamics, Pharmakokinetics, change in JAK2V617F clonal burden and bone marrow pathology, and quality of life improvements.

Study Status Information



Study Activation / Registration Date:

IRB Review and Approval Date:	06/30/2008

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	105

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Must be at least 18 years of age.

2) Confirmed diagnosis of polycythemia vera or essential thrombocythemia as determined by treating physician.

3) Patients should have disease refractory to hydroxyurea or for whom treatment with hydroxyurea is contraindicated as determined by the treating physician. Disease must be assessed within 21 days prior to treatment initiation overrall response (OR) Patients have refused further treatment with hydroxyurea due to side effects. These patients must have had a trial with hydroxyurea and the treating physician must concur that discontinuation of hydroxyurea is in the best interest of the patient

4) Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

5) Required baseline laboratory data include: a. Hct > 45% for PV or phlebotomy required two times in prior six months with at least one occurrence in prior three months b. Platelet count >/= 125 x 10^9/L for PV patients c. Platelet count > 650 x 10^9/L for ET unless receiving treatment

6) Continuation from Inclusion #5: d. Absolute neutrophil count (ANC) >/= 1.2 x 10^9/L for both patient groups e. Total bilirubin </= 2 x institutional upper limit of normal (ULN) for both patient groups f. Aspartate aminotransferase (AST) and alanine aminotransferase </= 2.5 x ULN for both patient groups g. Serum creatinine </= 2 x ULN for both patient groups

7) Females will be either postmenopausal for at least 1 year with documented follicle stimulating hormone (FSH) > 30 IU/L or surgically sterile for at least 3 months OR females of childbearing potential who must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from Screening through Follow-up. (Note: Permitted methods which are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed.)

8) Continuation from Inclusion #6: For all females, the urine pregnancy test result must be negative at Screening. Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from Screening through Follow-up. (Note: Permitted methods which are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed.)

9) Is able to comprehend and is willing to sign an informed consent form (ICF), indicating that the patient is aware of the nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomfort.

10) Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria:

1) Females who are pregnant or are currently breastfeeding.

2) Use of interferon alpha or anagrelide within 7 days or hydroxyurea within 1 day of enrollment. All other cytoreductive therapies for PV or ET or investigational medications must be discontinued within 28 days of enrollment.

3) Patients with a history of another malignancy. Exceptions to this rule are patients who had cervical intraepithelial neoplasia or basal or squamous cell skin cancer and have no evidence of recurrence. a. Patients with any cervical intraepithelial neoplasia or basal or squamous cell skin cancer occurring more than three years ago with no sequelae are eligible to enter the study. b. Patients with any cervical intraepithelial neoplasia or basal or squamous cell skin cancer occurring less than three years ago require medical monitor approval to enter the study.

4) Patients receiving therapy with intermediate high dose steroids greater than the equivalent of 10 mg of prednisone per day.

5) Patients with known active hepatitis A, B, or C, or known positivity for human immunodeficiency virus (HIV). (Active hepatitis is defined by presence of circulating viral antigens and/or viral RNA or DNA.)

6) Uncontrolled intercurrent illness or has any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.

7) Clinically significant cardiac disease New York Heart Association (NYHA Class III or IV)

8) Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks prior to study entry.

9) Presence of acute active infection requiring antimicrobials.

10) Prior treatment with any oral JAK inhibitor is not permitted unless agreed to by both the investigator and the Sponsor.

Links

Registration Number: NCT00726232
Study Information on Clinical Trials Registry (clinicaltrials.gov)