80 FR 30468 - Molecular Characterization of Multiple Myeloma Black/African Ancestry Disparity

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 102 (May 28, 2015)

Page Range		30468-30469
FR Document		2015-12742

The Food and Drug Administration (FDA) is announcing the availability of grant funds for the support of the efforts of the Center for Drug Evaluation and Research (CDER). FDA is announcing its intent to accept and consider a single-source application for the award of a grant to the Multiple Myeloma Service of Memorial Sloan Kettering Cancer Institute. The goal of the cooperative agreement between CDER and the Multiple Myeloma Service of Memorial Sloan Kettering Cancer Institute is to support the development of appropriate methodologies to conduct clinical trial design evaluation and determine extrapolation of findings from the general population to the U.S. Black population.

Federal Register, Volume 80 Issue 102 (Thursday, May 28, 2015)

[Federal Register Volume 80, Number 102 (Thursday, May 28, 2015)]
[Notices]
[Pages 30468-30469]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2015-12742]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-0012]

Molecular Characterization of Multiple Myeloma Black/African
Ancestry Disparity

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of grant funds for the support of the efforts of the
Center for Drug Evaluation and Research (CDER). FDA is announcing its
intent to accept and consider a single-source application for the award
of a grant to the Multiple Myeloma Service of Memorial Sloan Kettering
Cancer Institute. The goal of the cooperative agreement between CDER
and the Multiple Myeloma Service of Memorial Sloan Kettering Cancer
Institute is to support the development of appropriate methodologies to
conduct clinical trial design evaluation and determine extrapolation of
findings from the general population to the U.S. Black population.

DATES: Important dates are as follows:
1. The application due date is July 20, 2015.
2. The anticipated start date is August 2015.
3. The opening date is May 18, 2015.
4. The expiration date is July 21, 2015.

ADDRESSES: Submit electronic applications to: http://www.Grants.gov.
For more information, see section III of the SUPPLEMENTARY INFORMATION
section of this notice.

FOR FURTHER INFORMATION CONTACT: Dickran Kazandjian, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 2320, Silver Spring, MD 20993-0002, 240-
402-5272; or Vieda Hubbard, Division of Acquisition Support and Grants
(HFA-500), Food and Drug

[[Page 30469]]

Administration, 5630 Fishers Lane, Rockville, MD 20857, 240-402-7588.
For more information on this funding opportunity announcement (FOA)
and to obtain detailed requirements, please refer to the full FOA
located at: http://www.grants.gov. Search by Funding Opportunity
Number: RFA-FD-15-029.

SUPPLEMENTARY INFORMATION:

I. Funding Opportunity Description

RFA-FD-15-029
93.103

A. Background

Multiple Myeloma (MM) is mainly a disease of older adults with a
median diagnosis age of 65 years and patients younger than 40 represent
only 2 percent of diagnoses. In the United States, 20,000 new cases are
diagnosed annually. Although the etiology of MM remains elusive,
clinical features, observed racial disparity patterns of incidence,
reported familial clustering, and younger incidence in patients of
Black/African ancestry suggests a role for susceptibility genes. Novel
therapies have revolutionized treatment of MM and much of current
research is focused on identifying not only efficacious drugs but also
on the most efficacious time to initiate treatment. MM is a spectrum of
disease which is first manifested by its precursor state Monoclonal
gammopathy of undetermined significance (MGUS) which then evolves into
smoldering myeloma and then finally symptomatic myeloma and therefore
some paradigms of treatment initiation are evolving. Much of this work
involves identifying the molecular aberrations, which classify
patients' risks. However, this work has mostly been done on the
population as a whole. Despite that MM in patients of Black ancestry
clearly has a biologically different natural history; clinically Blacks
are assessed using the same genetic approaches as the whole population.
The proposed project will afford us the opportunity to identify and
characterize MM in the Black population with much higher genetic and
molecular resolution. It will answer questions such as whether Blacks
have, in general, better survival because of the presence of more low
risk genetic aberrations and whether these changes alter the effect of
treatment drug. Our conclusions may have immense regulatory impact. For
example, certain MM therapies may be indicated sooner in the treatment
course in Blacks. Alternatively, some therapies may be found to have
minimal efficacy and indication in Blacks with certain molecular
subtypes. This proposal will be the first study to characterize the
molecular subtypes of MM in Blacks in a systematic fashion, investigate
the effect of these on novel therapy outcomes, and potentially have
major impact on regulatory approvals of future therapies. Therefore, it
is imperative to focus on this under-represented population and at
least begin to understand the differences in MM pathophysiology, which
may ultimately lead to improved outcomes.
The Memorial Sloan Kettering Cancer Institute has established a
cohort of Black/African ancestry patients diagnosed with MM. These
patients have been previously enrolled onto clinical trials and bone
marrow biopsy tissue samples are available along with peripheral blood
samples all banked. Furthermore, there has been close monitoring of
these patients and detailed clinical data already exist. This is
crucial to the project. Memorial Sloan Kettering is uniquely positioned
to provide FDA much required data both by their novel technical
platform and also by their available unique patient cohort and biopsy
samples. Finally, organized involvement among a number of Sloan
Kettering/National Cancer Institute (NCI)/FDA working groups on issues
related to endpoints in MM which provides the unique ability to
collaboratively engage FDA, patients, academics, government and
industry so that any important findings may distributed to the
community will be required.

B. Research Objectives

The research objective is to characterize the molecular subtypes of
MM in patients of Black/African ancestry and investigate the effect of
these on prognosis and novel therapy outcomes.

C. Eligibility Information

The following organization is eligible to apply: The Multiple
Myeloma Service of the Memorial Sloan Kettering Cancer Institute. This
is a sole source request for application because the Multiple Myeloma
Service of the Memorial Sloan Kettering Cancer Institute is uniquely
situated to support FDA's scientific mission of protecting and
promoting the public health by initiating and facilitating research
into demographic subpopulations of the United States. It has both the
required patient population and the proprietary technical assays
required to perform the proposed work.

II. Award Information/Funds Available

A. Award Amount

It is anticipated that FDA/CDER will fund this Cooperative
Agreement up to $172,000 in Fiscal Year (FY) 2015 and $106,000 in FY
2016 in support of this program project. It is anticipated that only
one award will be made, not to exceed $278,000 (direct plus indirect)
for total costs. Awards are contingent upon the availability of funds.

B. Length of Support

Two-year period of performance beginning on August 2015 or date of
award.

III. Electronic Application, Registration, and Submission

Only one electronic application will be accepted. To submit an
electronic application in response to this FOA, the applicant should
first review the full announcement located at http://www.Grants.gov.
Search by Funding Opportunity Number: RFA-FD-15-029. (FDA has verified
the Web site addresses throughout this document, but FDA is not
responsible for any subsequent changes to the Web sites after this
document publishes in the Federal Register.) For the electronically
submitted application, the following steps are required.
Step 1: Obtain a Dun and Bradstreet (DUNS) Number
Step 2: Register With System for Award Management (SAM)
Step 3: Obtain Username & Password on http://www.Grants.gov
Step 4: Authorized Organization Representative (AOR)
Authorization
Step 5: Track AOR Status
Step 6: Register With Electronic Research Administration
(eRA) Commons
Steps 1 through 5, in detail, can be found at http://www07.grants.gov/applicants/organization_registration.jsp. Step 6, in
detail, can be found at https://commons.era.nih.gov/commons/registration/registrationInstructions.jsp. After you have followed
these steps, submit the electronic application to: http://
www.grants.gov.

Dated: May 20, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-12742 Filed 5-27-15; 8:45 am]
BILLING CODE 4164-01-P

30468 Federal Register / Vol. 80, No. 102 / Thursday, May 28, 2015 / Notices

The meropenem docket remained percent confidence interval, 78.5 to 89.2 http://www.fda.gov/Drugs/
opened for public comment from percent). DevelopmentApprovalProcess/
February 27, 2012, until March 28, Analysis of safety was a primary DevelopmentResources/ucm379088.htm
2012. There were no comments objective of the study. The following and in the docket (Ref. 1).
submitted to the docket during that assessments were included in the study: Dated: May 21, 2015.
time. The key findings of this final Monitoring for adverse events, serious
Leslie Kux,
clinical study report are: adverse events, and death;
documentation of seizures; acute Associate Commissioner for Policy.
The submitted study was an open-
abdominal complications; development [FR Doc. 2015–12848 Filed 5–27–15; 8:45 am]
label, non-comparative, multicenter,
prospective, multiple pharmacokinetic of resistant bacterial infection or BILLING CODE 4164–01–P

(PK) and safety study in infants less candidiasis; treatment failure; physical
than 91 days of age. The study enrolled examination; clinical laboratory values;
cultures from sterile sites, and DEPARTMENT OF HEALTH AND
200 infants with a median postnatal age HUMAN SERVICES
of 21 days (range 1 to 92 days) and a concomitant medications. There were
median gestation age (GA) of 27.8 weeks 11 deaths in the study; all occurred in
patients less than 32 weeks GA. The Food and Drug Administration
(range 22.5 to 40 weeks). Infants with
complicated intra-abdominal infections most common cause of death was multi- [Docket No. FDA–2015–N–0012]
who were receiving meropenem based organ failure. None of the deaths were
on local standard of care were eligible related to meropenem administration. Molecular Characterization of Multiple
for enrollment. Complicated intra- The following adverse events occurred Myeloma Black/African Ancestry
abdominal infections were defined per with a frequency in the study that Disparity
the protocol as physical, radiologic, or differed from that seen in previous
pediatric and adult studies: Convulsion AGENCY: Food and Drug Administration,
bacteriologic findings of complicated HHS.
intra-abdominal infection to include (seizures), 5 percent,
hyperbilirubinemia, 4.5 percent and ACTION: Notice.
peritonitis, necrotizing enterocolitis
(NEC) grade II or higher by Bell’s vomiting, 2.5 percent. Study oversight
SUMMARY: The Food and Drug
criteria, Hirschsprung’s disease with included a safety committee and an
Administration (FDA) is announcing the
perforation, spontaneous perforation, independent data safety monitoring
board. availability of grant funds for the
meconium ileus with perforation, bowel support of the efforts of the Center for
The Division of Anti-Infective
obstruction with perforation, as Drug Evaluation and Research (CDER).
Products agreed that meropenem was
evidenced by free peritoneal air on well-tolerated in the pediatric FDA is announcing its intent to accept
abdominal radiograph, intestinal population enrolled in the study. Of the and consider a single-source application
pneumatosis, or portal venous gas on 10 patients with seizures, 8 patients for the award of a grant to the Multiple
abdominal radiographic examination, or were adjudicated to have developed Myeloma Service of Memorial Sloan
possible NEC. seizures possibly due to the study Kettering Cancer Institute. The goal of
The study was not statistically medication. Because cerebrospinal fluid the cooperative agreement between
powered to establish efficacy because was only evaluated in a limited number CDER and the Multiple Myeloma
the Division of Anti-Infective Products of patients with seizures, it is not Service of Memorial Sloan Kettering
agreed that extrapolation of efficacy to possible to determine if the seizure Cancer Institute is to support the
pediatric populations from adult threshold may have changed due to development of appropriate
populations was acceptable. However, possible underlying meningitis and the methodologies to conduct clinical trial
clinical efficacy endpoints were also administration of meropenem. design evaluation and determine
evaluated. The efficacy assessment extrapolation of findings from the
included a comparison of the clinical II. Recommendation general population to the U.S. Black
status at study baseline and at day 28 or This study supports the use of population.
after a minimum of 7 days of treatment, meropenem in neonates and infants less DATES: Important dates are as follows:
using a combination of an assessment than 91 days of age for complicated 1. The application due date is July 20,
using the Score for Neonatal Acute intra-abdominal infections. However, 2015.
Physiology II tool and other protocol infants with complicated intra- 2. The anticipated start date is August
specified outcome criteria. The clinical abdominal infections are anticipated to 2015.
endpoint was defined as the patient have different physiological 3. The opening date is May 18, 2015.
being alive, with negative bacterial characteristics than patients with 4. The expiration date is July 21,
cultures from a sterile body fluid, and meningitis that may impact the PK of 2015.
a presumptive clinical cure. Clinical meropenem; as such, it may not be
failure was defined as death, change in appropriate to apply the PK findings ADDRESSES: Submit electronic
antibiotic therapy while on study drug, from this population to a patient applications to: http://www.Grants.gov.
or lack of presumptive clinical cure. The population with meningitis. The For more information, see section III of
addition of treatment directed against Division recommended that the the SUPPLEMENTARY INFORMATION section
Gram-positive pathogens from a non- evaluation of meropenem in infants less of this notice.
abdominal source was not considered to than 91 days of age be limited to the FOR FURTHER INFORMATION CONTACT:
asabaliauskas on DSK5VPTVN1PROD with NOTICES

represent treatment failure. Using these treatment of complicated intra- Dickran Kazandjian, Center for Drug
criteria, 195/200 patients or 97.5 percent abdominal infections at this time. Evaluation and Research, Food and
were considered to have achieved the FDA’s requested labeling changes, Drug Administration, 10903 New
clinical endpoint. Of the 195 patients including dosing recommendations for Hampshire Ave., Bldg. 22, Rm. 2320,
included in the efficacy population, 192 the use of meropenem in neonates and Silver Spring, MD 20993–0002, 240–
(98.5 percent) were evaluated for infants less than 91 days of age for 402–5272; or Vieda Hubbard, Division
efficacy. The overall efficacy success complicated intra-abdominal infections, of Acquisition Support and Grants
rate for the study was 84.4 percent (95 are available on the FDA Web site at (HFA–500), Food and Drug

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Document Created: 2018-02-21 10:32:52
Document Modified: 2018-02-21 10:32:52

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
Dates		Important dates are as follows:
Contact		Dickran Kazandjian, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2320, Silver Spring, MD 20993-0002, 240- 402-5272; or Vieda Hubbard, Division of Acquisition Support and Grants (HFA-500), Food and Drug Administration, 5630 Fishers Lane, Rockville, MD 20857, 240-402-7588.
FR Citation		80 FR 30468

80 FR 30468 - Molecular Characterization of Multiple Myeloma Black/African Ancestry Disparity

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 80, Issue 102 (May 28, 2015)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration