Controlled Study of Rigosertib Versus Physician's Choice of Treatment in MDS Patients After Failure of an HMA



Status:Recruiting
Conditions:Cancer, Blood Cancer, Blood Cancer, Anemia, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - 81
Updated:10/14/2018
Start Date:October 2015
End Date:September 2019
Contact:Joseph Morgan, MD
Email:jmorgan@onconova.us
Phone:(267) 759-3680

Use our guide to learn which trials are right for you!

A Phase III, International, Randomized, Controlled Study of Rigosertib Versus Physician's Choice of Treatment in Patients With Myelodysplastic Syndrome After Failure of a Hypomethylating Agent

The study's primary objective [in a population of patients with MDS after failure of
treatment with azacitidine (AZA) or decitabine (DAC)], is to compare the overall survival
(OS) of patients in the rigosertib group vs the Physician's Choice group, in all patients and
in a subgroup of patients with IPSS-R very high risk.

This is a Phase III, open-label, randomized, controlled, international study. Approximately
360 patients < 82 years of age with MDS classified as RAEB-1, RAEB-2, or RAEB-t who received
AZA or DAC for ≤ 9 months and/or ≤ 9 cycles over 12 months and had their last dose of AZA or
DAC within 6 months prior to screening will be stratified by:

- Very high risk (VHR) vs non-VHR per IPSS-R, and

- Geographic region (North America vs Europe vs Asia; because approved products and
standard of care may vary by region), and randomly assigned in a 2:1 ratio to one of the
following 2 treatment groups:

- Rigosertib 1800 mg/24 hr administered as a 72 hr CIV infusion on Days 1, 2, and 3 of a 2
week cycle for the first 8 cycles, and on Days 1, 2, and 3 of a 4-week cycle thereafter
(N = approximately 240 patients);

- Physician's Choice of alternative treatment, which may include any approved or
standard-of-care therapy that the patient has not shown to be hypersensitive to, based
on frequently used treatment for MDS, as per institutional guidelines, after receipt of
HMAs (N = approximately 120 patients). The drugs used in the Physician's Choice arm
should be used according to the recommendations, if clinically appropriate, provided in
the corresponding Summary of Product Characteristics (SmPC) and Prescribing Information
of these drugs. Experimental therapies are not allowed on the PC arm.

Patients will be treated until 2006 IWG progression criteria are met (ie, 50% increase of BM
blasts or worsening of cytopenias) or until an unacceptable toxicity or intolerance.

For all randomized patients who discontinue study treatment, subsequent therapies with their
start and end dates, as well as survival time after treatment discontinuation, will be
documented at least monthly until death.

Patients in the PC group who progress will not be allowed to cross over to rigosertib.

All patients in both treatment groups will be allowed, as medically justified, access to RBC
and platelet transfusions and to growth factors (granulocyte colony-stimulating factor
(G-CSF), erythropoietin, and thrombopoietin).

Inclusion Criteria:

- MDS classified as follows:

- RAEB-1 per World Health Organization (WHO) MDS criteria (5% to <10% BM blasts)

- RAEB-2 per WHO MDS criteria (10% to <20% BM blasts)

- RAEB-t per French-American-British (FAB) classification (20% to 30% BM blasts)

- At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin
[Hgb] < 10 g/dL)

- Progression (according to 2006 IWG criteria) at any time after initiation of AZA or
DAC treatment or Failure to achieve complete or partial response or hematological
improvement (HI) (according to 2006 IWG) after at least six 4-week cycles of AZA or
either four 4-week or four 6-week cycles of DAC administered or Relapse after initial
complete or partial response or HI (according to 2006 IWG criteria)

- Duration of prior HMA therapy ≤ 9 months and/or total ≤ 9 cycles of prior HMA therapy
in ≤ 12 months

- Last dose of AZA or DAC within 6 months before the planned date of randomization;
however, must be off these treatments for ≥ 4 weeks before randomization

- Has failed to respond to, relapsed following, not eligible for, or opted not to
participate in allogeneic stem cell transplantation

- Off all treatments for MDS (including AZA and DAC) for ≥ 4 weeks before randomization;
growth factors (G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed
before and during the study as clinically indicated

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

- Willing to adhere to protocol prohibitions and restrictions

- Patient must sign informed consent form to indicate patient's understanding study's
purpose and procedures and willingness to participate. Should patient be incapable of
giving consent, the patient's legally authorized representative (as defined by local
regulation) must give consent. However, should patient, in any manner, choose not to
participate this takes precedence and will be respected.

- Patients with 5q- syndrome should have failed to respond to or progressed on treatment
with lenalidomide, where available and indicated

Exclusion Criteria:

- Previous participation in a clinical study of IV or oral rigosertib; patients who
failed screening for other rigosertib studies may be screened for participation

- Eligible to receive induction chemotherapy, such as 7-10 days of cytosine arabinoside
plus 2-3 days of an anthracycline, or high-dose cytarabine

- Suitable candidate to receive allogeneic stem cell transplantation; patient is
eligible for study if a suitable candidate refuses to undergo an allogeneic stem cell
transplant or a suitable donor cannot be found

- Any active malignancy within the past year, except basal cell or squamous cell skin
cancer or carcinoma in situ that is unlikely to progress in two years

- Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure or unstable angina pectoris

- Active infection not adequately responding to appropriate therapy

- Total bilirubin ≥1.5 mg/dL not related to hemolysis or Gilbert's disease

- Alanine transaminase (ALT)/aspartate transaminase (AST) ≥2.5 x upper limit of normal
(ULN)

- Serum creatinine ≥2.0 mg/dL or eGFR (estimated Glomerular Filtration Rate) < 40
mL/min.

- Known active HIV, hepatitis B or hepatitis C, where active is defined as follows:

- HIV or hepatitis C - presence of viral load

- Hepatitis B - antigen positive

- Uncorrected hyponatremia (defined as serum sodium value of <130 mEq/L)

- Female patients of child-bearing potential and male patients with sexual partners of
child-bearing potential who are unwilling to follow strict contraception requirements
before entry and throughout the study, up to and including the 30-day non-treatment
follow-up period. Examples of acceptable contraception methods include:

- estrogen-gestagen based contraceptives associated with inhibition of ovulation
(oral, intravaginal, transdermal),

- gestagen-only based contraceptives associated with inhibition of ovulation (oral,
injectable, implantable),

- intra-uterine devices (IUDs),

- intra-uterine hormone-releasing systems (IUSs),

- bilateral tubal occlusion

- vasectomized partner

- sexual abstinence in accordance with an individual's lifestyle

- Female patients of child-bearing potential (pre-menopausal and not surgically
sterilized) who are breast-feeding or have a positive blood beta-human chorionic
gonadotropin pregnancy test at Screening

- Major surgery without full recovery or within 3 weeks before planned randomization;

- Uncontrolled hypertension

- New onset seizures (within 3 months before planned randomization) or poorly controlled
seizures

- Any other concurrent investigational agent or chemotherapy, radiotherapy,
immunotherapy, or corticosteroids (prednisone up to 20 mg/day or its equivalent is
permitted for chronic conditions)

- Treatment with cytarabine at any dose, lenalidomide, or any other therapy targeted to
the treatment of MDS (other than growth factors and other supportive care measures)
within 4 weeks of planned randomization

- Investigational therapy within 4 weeks of planned randomization

- Psychiatric illness or social situation that would limit the patient's ability to
tolerate and/or comply with study requirements.

- Patient previously diagnosed with AML (defined as a bone marrow or peripheral blood
blast percentage of >30%).
We found this trial at
43
sites
Indianapolis, Indiana 46202
Principal Investigator: S. Hamid Sayar, MD
?
mi
from
Indianapolis, IN
Click here to add this to my saved trials
800 Washington St
Boston, Massachusetts 02111
(617) 636-5000
Principal Investigator: Kellie Sprague, MD
Tufts Medical Center Tufts Medical Center is an internationally-respected academic medical center – a teaching...
?
mi
from
Boston, MA
Click here to add this to my saved trials
3400 Spruce St
Philadelphia, Pennsylvania 19104
 (215) 662-4000
Principal Investigator: Selina Luger, MD
Hospital of the University of Pennsylvania The Hospital of the University of Pennsylvania (HUP) is...
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
40 Sunshine Cottage Road
Valhalla, New York 10595
(914) 594-4000
Principal Investigator: Karen Seiter, MD
New York Medical College The College was founded in 1860 by a group of New...
?
mi
from
Valhalla, NY
Click here to add this to my saved trials
Albuquerque, New Mexico 87131
Principal Investigator: Cecilia Arana Yi, MD
?
mi
from
Albuquerque, NM
Click here to add this to my saved trials
22 South Greene Street
Baltimore, Maryland 21201
410-328-7904
Principal Investigator: Maria R. Baer, MD
University of Maryland Greenebaum Cancer Center The University of Maryland Marlene and Stewart Greenebaum Cancer...
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Bethesda, Maryland 20817
Principal Investigator: Ralph V. Boccia, MD
?
mi
from
Bethesda, MD
Click here to add this to my saved trials
Charlottesville, Virginia 22903
Principal Investigator: Michael Keng, MD
?
mi
from
Charlottesville, VA
Click here to add this to my saved trials
1653 W. Congress Parkway
Chicago, Illinois 60612
(312) 942-5000
Principal Investigator: Jamile Shammo, MD
Rush University Medical Center Rush University Medical Center encompasses a 664-bed hospital serving adults and...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
5841 S Maryland Ave
Chicago, Illinois 60637
(773) 702-1000
Principal Investigator: Lucy A. Godley, MD, PhD
University of Chicago Medical Center The University of Chicago Medicine has been at the forefront...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
1801 West Taylor, Suite 1E
Chicago, Illinois 60612
312.355.1625
Principal Investigator: Irum Khan, MD
University of Illinois Cancer Center The University of Illinois Cancer Center is dedicated to reducing...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Dallas, Texas 75201
Principal Investigator: Vikas Bhushan, MD
?
mi
from
Dallas, TX
Click here to add this to my saved trials
2201 Inwood Rd
Dallas, Texas 75235
(214) 645-8300
Principal Investigator: Prapti Patel, MD
U.T. Southwestern Medical Center The story of UT Southwestern Medical Center is one of commitment...
?
mi
from
Dallas, TX
Click here to add this to my saved trials
Darlinghurst, New South Wales 2010
Principal Investigator: David Ma, MD
?
mi
from
Darlinghurst,
Click here to add this to my saved trials
2799 W Grand Blvd
Detroit, Michigan 48202
(313) 916-2600
Principal Investigator: Steven Gamalski, MD
Henry Ford Hospital Founded in 1915 by auto pioneer Henry Ford and now one of...
?
mi
from
Detroit, MI
Click here to add this to my saved trials
Fleming Island, Florida 32003
Principal Investigator: Mehdi Moezi, MD
?
mi
from
Fleming Island, FL
Click here to add this to my saved trials
Flemington, New Jersey 08822
Principal Investigator: Kenneth Blankstein, MD
?
mi
from
Flemington, NJ
Click here to add this to my saved trials
Gainesville, Florida 32608
Principal Investigator: Christopher R. Cogle, MD
?
mi
from
Gainesville, FL
Click here to add this to my saved trials
Greenville, South Carolina 29605
Principal Investigator: Suzanne R. Fanning, DO
?
mi
from
Greenville, SC
Click here to add this to my saved trials
92 2nd St
Hackensack, New Jersey 07601
(201) 996-5900
Principal Investigator: James McCloskey II, MD
John Theurer Cancer Center at the Hackensack University Medical Center The mission of the John...
?
mi
from
Hackensack, NJ
Click here to add this to my saved trials
Houston, Texas 77030
Principal Investigator: Guillermo Garcia-Manero, MD
?
mi
from
Houston, TX
Click here to add this to my saved trials
3855 Health Sciences Dr,
La Jolla, California 92093
(858) 822-6100
Principal Investigator: Rafael Bejar, MD, PhD
UC San Diego Moores Cancer Center Established in 1978, UC San Diego Moores Cancer Center...
?
mi
from
La Jolla, CA
Click here to add this to my saved trials
Lake Success, New York 11042
Principal Investigator: Steven Allen, MD
?
mi
from
Lake Success, NY
Click here to add this to my saved trials
Lancaster, Pennsylvania 17601
Principal Investigator: Hyatt P. (Tracy) DeGreen III, DO
?
mi
from
Lancaster, PA
Click here to add this to my saved trials
757 Westwood Plaza
Los Angeles, California 90024
(310) 825-9111
Principal Investigator: Gary J. Schiller, MD
UCLA Medical Center Founded in 1955, UCLA Medical Center became Ronald Reagan UCLA Medical Center...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
1441 Eastlake Ave
Los Angeles, California 90033
(323) 865-3000
Principal Investigator: Casey O'Connell, MD
U.S.C./Norris Comprehensive Cancer Center The USC Norris Comprehensive Cancer Center, located in Los Angeles, is...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
Madison, Wisconsin 53792
Principal Investigator: Ryan Mattison, MD
?
mi
from
Madison, WI
Click here to add this to my saved trials
1000 N Oak Ave
Marshfield, Wisconsin 54449
(715) 387-5511
Principal Investigator: Richard John Mercier, MD
Marshfield Clinic - Marshfield Center The Clinic was incorporated under Wisconsin law in 1916 and...
?
mi
from
Marshfield, WI
Click here to add this to my saved trials
Maywood, Illinois 60153
Principal Investigator: Patrick J. Stiff, MD
?
mi
from
Maywood, IL
Click here to add this to my saved trials
Minneapolis, Minnesota 55455
Principal Investigator: Erica Warlick, MD
?
mi
from
Minneapolis, MN
Click here to add this to my saved trials
New Brunswick, New Jersey 08903
Principal Investigator: Dale Schaar, MD, PhD
?
mi
from
New Brunswick, NJ
Click here to add this to my saved trials
New Orleans, Louisiana 70112
Principal Investigator: Hana Safah, MD
?
mi
from
New Orleans, LA
Click here to add this to my saved trials
630 W 168th St
New York, New York
212-305-2862
Principal Investigator: Mark Heaney, MD
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10029
Principal Investigator: Lewis R. Silverman, MD
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10021
Principal Investigator: Gail J. Roboz, MD
?
mi
from
New York, NY
Click here to add this to my saved trials
Ogden, Utah 84403
Principal Investigator: Vincent L. Hansen, MD
?
mi
from
Ogden, UT
Click here to add this to my saved trials
Orange City, Florida 32763
Principal Investigator: Santosh Nair, MD
?
mi
from
Orange City, FL
Click here to add this to my saved trials
5501 Old York Road
Philadelphia, Pennsylvania 19141
Principal Investigator: Claudia M. Dourado, MD
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Plainville, Connecticut
Principal Investigator: Wylie D. Hosmer, MD
?
mi
from
Plainville, CT
Click here to add this to my saved trials
223 N Van Dien Ave
Ridgewood, New Jersey 07450
(201) 447-8000
Principal Investigator: Jason Suh, MD
The Valley Hospital The Valley Hospital is a fully accredited, acute care, not-for-profit hospital serving...
?
mi
from
Ridgewood, NJ
Click here to add this to my saved trials
Rochester, Minnesota 55905
Principal Investigator: Aref Al-Kali, MD
?
mi
from
Rochester, MN
Click here to add this to my saved trials
825 Eastlake Avenue East
Seattle, Washington 98109
Principal Investigator: Bart Scott, MD
?
mi
from
Seattle, WA
Click here to add this to my saved trials
Westwood, Kansas 66205
Principal Investigator: Abdulraheem M. Yacoub, MD
?
mi
from
Westwood, KS
Click here to add this to my saved trials