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A Phase I Trial of Ipilimumab (Immunotherapy) and Imatinib Mesylate (c-Kit Inhibitor) in Patients With Advanced Malignancies

Phase 1
15 Years
Open (Enrolling)
Advanced Cancers

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Trial Information

A Phase I Trial of Ipilimumab (Immunotherapy) and Imatinib Mesylate (c-Kit Inhibitor) in Patients With Advanced Malignancies

Study Groups:

Dose Escalation Group:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of your study drug combination based on when you joined this study. Up to 4 dose
levels of the study drug combination will be tested. Up to 6 participants will be enrolled
at each dose level. The first group of participants will receive the lowest dose level.
Each new group will receive a higher dose than the group before it, if no intolerable side
effects were seen. This will continue until the highest tolerable dose of the study drug
combination is found.

Dose Expansion Group:

After the highest tolerable dose level of the study drug combination is found, up to 20
additional participants will be enrolled in the dose expansion group. Patients with
metastatic gastrointestinal stromal tumors (GIST), melanoma, or tumors with original tumor
biopsies testing positive for KIT mutations (a cancer biomarker) will be eligible to enroll
and will receive the highest dose of the study drug combination that was tolerated in the
dose escalation group.

Study Drug Administration:

If you are in the Dose Escalation Group, the first study cycle is 35 days. Each cycle after
that is 21 days.

If you are in the Dose Expansion Group, all study cycles are 21 days.

If you are in the Dose Escalation Group, you will start taking imatinib by mouth 1 time each
day for 14 days before you receive ipilimumab. On Day 15 of each cycle, you will receive a
single dose of ipilimumab by vein over 90 minutes. You will continue to take imatinib by
mouth 1 time each day.

If you are in the Dose Expansion Group, you will receive ipilimumab by vein over 90 minutes
on Day 15 of each cycle. You will also take imatinib by mouth 1 time each day of each

Study Visits:

One (1) time each week during Cycle 1:

- You will have a physical exam, including measurement of your weight and vital signs.

- You will be asked about any drugs you may be taking and any side effects you may be

- Blood (about 1 tablespoon) will be collected for routine tests.

- Urine will be collected for routine tests (only during the first week of Cycle 1).

Every 3 weeks during Cycles 2 and beyond:

- You will have a physical exam, including measurement of your weight and vital signs.

- Blood (about 1 tablespoon) and urine will be collected for routine tests.

Starting after Cycle 2:

- You will have a CT or MRI scan after every 2 cycles to check the status of the disease.

- If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine
pregnancy test.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

This is an investigational study. Ipilimumab is FDA approved and commercially available for
the treatment of unresectable or metastatic melanoma. Imatinib is FDA approved and
commercially available for the treatment of advanced or metastatic gastrointestinal stromal
tumor (GIST).

The combination of ipilimumab and imatinib is currently being used for research purposes

Up to 96 participants will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. For dose escalation study, patients must have histological confirmation of solid
tumors that is metastatic or unresectable. For expansion cohorts, patients must have
metastatic or unresectable GIST, melanoma, or uncategorized tumors that are positive
for c-KIT mutations. KIT positive tumors will be confirmed in original biopsied
tumors and biopsied tumors acquired during this study. This analysis will be done by
CLIA approved mutational analysis which will likely include isolation of genomic DNA
from tumor, polymerase chain reaction (PCR) amplification of exons of interest of
c-KIT gene, bidirectional sequencing of PCR amplicons, and computational analysis of
sequences to determine mutation presence or absence.

2. Patients who have completed previous therapies 4-weeks prior to (or within 5 drug
half lives) enrollment on study. Radiation therapy wash out period will be 2 weeks.
This includes an exception of patients with metastatic GIST tumors who are taking
maintenance imatinib mesylate therapy. These patients are allowed to remain on
imatinib mesylate therapy up to enrollment in this study.

3. Age > or = 15 years

4. ECOG performance status < 2 (Karnofsky > 60%).

5. Patients must have normal organ and marrow function as defined below: leukocytes >
3,000/mcL; absolute neutrophil count >1,500/mcL; platelets > 100,000/mcL, total
bilirubin < or = 2.0 mg/dL. (Does NOT apply to patients with Gilbert's Syndrome);
AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal (patients with liver
involvement will be allowed < or = 5.0 X institutional upper normal limit) serum
creatinine < 2.0 mg/dL

6. Patients MUST have recovered from all treatment related toxicities to Grade 1 NCI
CTCAE (v 4.0) in severity

7. Patients must be willing and able to review, understand, and provide written consent
before starting therapy

8. Patients with histologically proven intracranial glioblastoma, gliosarcoma or
anaplastic astrocytoma will be eligible. Patients must have shown unequivocal
radiographic evidence for tumor progression by MRI scan. A scan should be performed
within 14 days prior to registration and on a steroid dose that has been stable for
at least 5 days. If the steroid dose is increased between the date of imaging and
registration, a new baseline MRI is required.

Exclusion Criteria:

1. Autoimmune disease: Patients with a history of inflammatory bowel disease (including
Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid
arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus
or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this

2. History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal
carcinomatosis or other known risk factors for bowel perforation.

3. Any underlying medical or psychiatric condition, which in the opinion of the
Investigator, will make the administration of study drug hazardous or obscure the
interpretation of Adverse Events (AEs): e.g. a condition associated with frequent
diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the
patient has not recovered, or partial endocrine organ deficiencies.

4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, history of congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

5. Known HIV, Hepatitis B, or Hepatitis C.

6. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up
to one month prior to or after any dose of ipilimumab).

7. Concomitant therapy with any of the following: IL-2, interferon or other non-study
immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other
investigational therapies; or chronic use of systemic corticosteroids (used in the
management of cancer or non-cancer-related illnesses).

8. Patients who do not agree to practice appropriate birth control methods while on

9. Pregnant women are excluded from this study. Women of child-bearing potential and men
must agree to use contraception prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) of Ipilimumab and Imatinib Mesylate

Outcome Description:

Maximum tolerated dose (MTD) defined as highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort.

Outcome Time Frame:

56 days

Safety Issue:


Principal Investigator

David S. Hong, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

February 2013

Completion Date:

Related Keywords:

  • Advanced Cancers
  • Advanced Cancers
  • Advanced Malignancies
  • Metastatic
  • Unresectable
  • Ipilimumab
  • Yervoy
  • BMS-734016
  • MDX010
  • Imatinib Mesylate
  • Imatinib
  • Gleevec
  • STI 571
  • NSC-716051
  • Neoplasms



UT MD Anderson Cancer Center Houston, Texas  77030