Pomalidomide in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 2 May 2022
• Main ID: NCT02415153
• Date of registration: 13/04/2015
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Pomalidomide in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors
• Scientific title: A Phase I Trial of Pomalidomide for Children With Recurrent, Progressive, or Refractory CNS Tumors
• Date of first enrolment: July 14, 2015
• Target sample size: 29
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02415153
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Jason R Fangusaro
• Affiliation: Pediatric Brain Tumor Consortium

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients must have received standard therapy (or generally accepted upfront therapy if
no standard exists) and have no known curative therapy

- Patients with a histologically confirmed diagnosis of a primary CNS tumor that is
recurrent, progressive or refractory to standard therapy; refractory disease will be
defined as the presence of persistent abnormality on conventional magnetic resonance
imaging (MRI) imaging that is further distinguished by histology (biopsy or sample of
lesion) or advanced imaging, OR as determined by the treating physician and discussed
with the primary investigator prior to enrollment; all tumors must have histological
verification at either the time of diagnosis or recurrence except for patients with
diffuse intrinsic brain stem tumors or optic pathway gliomas; patients with
neurofibromatosis type-I (NF-1) associated CNS tumors are eligible if they meet all
other eligibility criteria

- Patients must have evaluable disease on MRI imaging

- Patients must have body surface area (BSA) > 0.55 m^2 at the time of enrollment

- In the event of de-escalation from dose level 1 to dose level 0, patients with
BSAs < 0.67 m^2 are not eligible

- Patients must have recovered from clinically significant, acute, treatment-related
toxicities of prior therapies; for those acute baseline adverse events attributable to
prior therapy, recovery is defined as a toxicity grade =< 2, using Common Terminology
Criteria for Adverse Events (CTCAE) version (v) 4.0, unless otherwise specified in the
inclusion and exclusion criteria

- Agents that potentially fit into more than one category or do not clearly fit
into any category listed above should be discussed with the study principal
investigator (PI) prior to enrollment

- Patients must have received their last dose of known myelosuppressive anticancer
therapy greater than 28 days prior to study enrollment or > 42 days if nitrosourea

- Patients must have received their last dose of any other investigational agent greater
than 28 days prior to enrollment (with exception of fluorothymidine F-18 [FLT])

- Patients must have received their last dose of any other biologic agent greater
than 7 days prior to enrollment

- Patients must have received their last dose of any other biologic agent greater than 7
days prior to enrollment

- For agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur and discussed with the PI

- Monoclonal antibody treatment and agents with known prolonged half-lives: at least
three half-lives must have elapsed prior to enrollment

- Immunomodulatory therapy: greater than 28 days must have elapsed since last dose of an
immune modulating agent, including vaccine therapy

- Administration of the radioisotope, 18-FLT, which is being concurrently investigated
on an imaging study within the Pediatric Brain Tumor Consortium (PBTC), is allowed >
72 hours prior to initiation of pomalidomide on this study; any adverse events related
to the FLT must have resolved completely

- Patients must have had their last fraction of:

- Craniospinal irradiation, total body irradiation (TBI), or >= 50% radiation of
pelvis > 3 months prior to enrollment

- Focal irradiation > 6 weeks prior to enrollment

- Local palliative radiation therapy (XRT) (small port) >= 4 weeks

- Patient must be:

- >= 6 months since allogeneic bone marrow transplant prior to enrollment

- >= 3 months since autologous bone marrow/stem cell prior to enrollment

- >= 3 months since stem cell transplant or rescue without TBI with no graft vs.
host disease prior to enrollment

- No graft versus host disease

- Patients on anticonvulsant therapy may continue these at the discretion of their
treating physician; however, it is recommended that anticonvulsant levels be checked
periodically as clinically indicated if possible

- Patients on alternative supplements should strongly be encouraged to discontinue them
prior to enrollment; if they opt to continue, they may enroll on study as long as they
have been receiving the supplement for at least 30 days, there is NO evidence of
hepatic, renal or other organ dysfunction, administration is approved by the PI, and
administration is documented in the study diary

- Patients must be on a stable or decreasing dose of corticosteroids for 5 days prior to
enrollment; patient may be taking therapeutic doses of steroids during the initial
dose escalations and prior to defining an RP2D; this should be recorded in the
database; once the RP2D has been established, enrollment may be limited based on
steroid use;*physiologic replacement doses will be defined on this protocol as no more
than 0.75 mg/m^2/day of dexamethasone or equivalent of steroids; doses higher than
this will be considered therapeutic

- All races and ethnic groups are eligible for this study

- Patients should have no significant worsening in clinical status for a minimum of 2
days prior to enrollment

- Patients must be able to swallow whole capsules

- Patients should undergo a repeat MRI prior to enrollment if there is a significant
worsening or new neurologic symptoms in the interval between the eligibility scan and
start of protocol therapy

- The repeat scan will act as a new baseline and the eligibility scan for these
patients

- Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score
(LPS for =< 16 years of age) assessed within 14 days of enrollment must be >= 50

- Absolute neutrophil count >= 1,000/mm^3

- Platelets >= 100,000/mm^3 (unsupported, defined as no platelet transfusion within 7
days and recovery from nadir)

- Hemoglobin >= 8 g/dL (may receive transfusions)

- Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)

- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
institutional upper limit of normal

- Albumin >= 3 g/dL

- Serum creatinine based on age/gender as noted; patients that do not meet the criteria
below but who have a 24-hour creatinine clearance or glomerular filtration rate (GFR)
(radioisotope or iothalamate) >= 70 ml/min/1.73 m^2 are eligible




Age minimum: 3 Years
Age maximum: 20 Years
Gender: All

Health Condition(s) or Problem(s) studied

Recurrent Childhood Brain Stem Glioma

Recurrent Childhood Visual Pathway Glioma

Neurofibromatosis Type 1

Refractory Primary Central Nervous System Neoplasm

Recurrent Primary Central Nervous System Neoplasm

Intervention(s)

Drug: Pomalidomide

Other: Pharmacological Study

Other: Laboratory Biomarker Analysis

Primary Outcome(s)

Pharmacokinetics parameters of pomalidomide [Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose day 1 of course 1; 1 sample pre-dose any day between days 3-21 of course 1]

Maximum tolerated dose/recommended phase II dose of pomalidomide [Time Frame: Up to 28 days]

Secondary Outcome(s)

Event-free survival [Time Frame: The time from study enrollment until the time of progressive disease, second-(ary) malignancy or death from any cause on study treatment, assessed up to 2 years]

Duration of response [Time Frame: The time from the initial documented response (complete response, partial response or long-term stable disease) to the first confirmed progressed disease, assessed up to 2 years]

Response rate (complete response, partial response, and stable disease) [Time Frame: Up to 2 years]

Secondary ID(s)

UM1CA081457

CC-4047-PBTC-043

PPBTC-043_R04PAPP01

PBTC-043

NCI-2014-02182

Source(s) of Monetary Support

Please refer to primary and secondary sponsors