MDACC Study Summary 2008-0275

Study Summary
No. 2008-0275:.......Hematologic Disorder......Srdan Verstovsek......Leukemia

Study Summary Title



Study Summary Number:	2008-0275

Study Title:	A 24-week with possible extension, prospective, multicentre, randomized, double blind, placebo-controlled, 2-parallel group with a randomization 1:1, Phase III study to compare efficacy and safety of masitinib at 6 mg/kg/day to placebo in treatment of patients with Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis with handicap

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:	Hematologic Disorder	Supported By:	AB Science

Phase of Study:	Phase III	Return Visit:	Eligible patients will be treated with masitinib or matching placebo for 24 weeks with possible extension. Patients will be seen every 4 Weeks.

Treatment Agents:	Masitinib	Home Care:	Self Medicated

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 compare the benefits of treatment with masitinib to no treatment in patients with mastocytosis with handicap.

Study Objectives / Outcomes

The objective of this study is to compare the efficacy and safety of masitinib at 6 mg/kg/day to placebo in the treatment of patients with mastocytosis with handicap based on treatment effect on the pruritus score, the number of flushes per week, the Hamilton score, and the Fatigue Impact scale.

Definition of: Response (improvement of >/=50% in at least one handicap: pruritis score, number of flushes per week, Hamilton score, Fatigue Impact Scale score)

Primary endpoint:

Responder rate at week 24

Secondary endpoint:

Response (success) in at least two out of three variables among pruritus, flushes, depression or Asthenia at week 12 and week 24
Pruritus score at week 12 and week 24
Number of flushes per week at week 12 and week 24
Hamilton score at week 12 and week 24
Fatigue Impact Scale at week 12 and week 24
Number of mictions per day at week 12 and week 24
Number of stools per day at week 12 and week 24
Number of anaphylactoid shocks at week 12 and week 24
QLQ C-30 scores at week 12 and week 24
Overall Patient Assessment (OPA) at week 12 and week 24
AFIRMM V2 score at week 12 and week 24
Percentage of patient without handicap at week 24
Mast cell infiltration in the skin or bone marrow at week 24
Serum tryptase level at week 24

Clinical and biological safety profile (including occurrence of Adverse Events, the potential changes in vital signs, EKG, Chest X-Ray and biological parameters)

Study Status Information



Study Activation / Registration Date:	08/27/2009

IRB Review and Approval Date:	08/26/2008

Study Type:	Phase Iii

Recruitment Status:	Open

Projected Accrual:	200

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) Patient with one of the following documented mastocytosis: Smouldering Systemic, Mastocytosis, Indolent Systemic Mastocytosis, Cutaneous Mastocytosis.

2) Patient with documented mastocytosis and evaluable disease based upon histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin and/or bone marrow biopsy

3) Patient with documented treatment failure of his/her handicap(s) with at least one of the following therapy used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor, Osteoclast inhibitor, Cromoglycate sodium, Antileukotriene, Other therapies used for the symptomatic care. These therapies should be maintained at the same dose during the study. No change in the symptomatic treatment of mastocytosis or administration of any new treatment of mastocytosis should occur.

4) Handicapped status defined as at least two of the following handicaps, including at least one among pruritus, flushes, depression and asthenia: pruritus score >/= 6, number of flushes per week >/= 7, Hamilton rating scale (depression) >/= 10, number of stools per day >/= 4, number of mictions per day >/=8, Fatigue Impact Scale total score (asthenia) >/= 40.

5) Patient with OPA >/= 2 (moderate to intolerable general handicap). 1-None; 2-Mild; 3-Moderate; 4-Severe; 5-Intolerable

6) ECOG </= 2

7) Patient with adequate organ function : absolute neutrophil count (ANC) >/= 2.0 x 10^9/L, platelets (PTL) >/= 100 x 10^9/L, AST/ALT </= 2.5x ULN (</= 5 x ULN in case of liver mast cell involvement), bilirubin </= 1.5x ULN, creatinine </= 1.5 x ULN, albumin > 0.75 x LLN, urea </= 1.5 x ULN, negative proteinuria defined as negative dipstick; in case of the positive dipstick (proteinuria equal to or greater than 30 mg/dL), 24 hours proteinuria < 1.5g/24 hours.

8) Subjects must be >/= 18 years of age.

9) Men and women of child bearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test) must agree to use 2 methods of medically acceptable forms of contraception during the study. Men and women of childbearing potential must agree using contraception for three months following their participation in the study

10) Patient should be able and willing to comply with study visits and procedures per protocol.

11) Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.

12) Patient must be covered by insurance for routine costs (applicable to European patients only).

Exclusion Criteria:

1) Patient with one of the following mastocytosis: Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM).

2) Previous treatment with any tyrosine kinase Inhibitor.

3) Patient who underwent major surgery within 2 weeks prior to study enrolment.

4) Vulnerable population defined as : Life expectancy < 6 months, Patient with < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ, Patient with grade III/IV cardiac conditions as defined by the New York Heart Association Criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study), Patient with any severe and/or uncontrolled medical condition, Patient with known diagnosis of human immunodeficiency virus (HIV) infection.

5) Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.

6) Patient with any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events.

7) Previous treatments: Change in the symptomatic treatment of mastocytosis or administration of any new treatment of mastocytosis within 4 weeks prior to baseline.

8) Treatment with any investigational agent within 4 weeks prior to baseline.

Links

Registration Number: NCT00814073
Study Information on Clinical Trials Registry (clinicaltrials.gov)