Phase I Trial of Cabozantinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT01961765 | Completed Phase 1 DMC

• 1 other identifier: 13-363
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is evaluating a drug called cabozantinib as a possible treatment for acute myeloid leukemia (AML). This research study is a Phase I clinical trial. Phase I trials test the safety of an investigational drug or combination of drugs. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. This means that the FDA has not approved giving cabozantinib for use in patients, including patients with your type of cancer. The study drug cabozantinib works by inhibiting several different proteins which are believed to be involved in the growth and multiplication of the cancerous cells associated with acute myeloid leukemia. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to prevent cancer growth. The primary purpose of this research study is to determine the highest dose of Cabozantinib that can safely be given without severe or unmanageable side effects. The dose identified in this study will be used in future research studies that seek to determine the role of cabozantinib as a treatment for AML.

Conditions

Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Keywords

Relapsed acute myeloid leukemia; Refractory acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of cabozantinib in patients with advanced acute myeloid leukemia

  To define the maximum tolerated dose (MTD) of cabozantinib in patients with advanced acute myeloid leukemia

  2 Years

Secondary Outcomes (6)

• Number of patients with adverse events including grade 3/4 adverse events

  2 Years

• Response rate

  2 Years

• Progression-free survival after treatment

  2 Years

• Pharmacodynamic effects of MET and FLT3 inhibition

  2 Years

• Rate of disease remission

  2 years

Study Arms (1)

cabozantinib

EXPERIMENTAL

Cabozantinib will be administered at a dose of 40mg daily by mouth in the first cohort. Dose escalation will occur in subsequent patient cohorts. We will evaluate 3-6 patients per dose level.

Drug: cabozantinib

Interventions

cabozantinib DRUG

cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults, 18 years of age and older, with pathologically confirmed, relapsed or refractory acute myelogenous leukemia OR those 70 and older who are not candidates for, or decline, conventional front line chemotherapy.
• White blood cell count (WBC) should be lower than 30,000/mm3 prior to initiation of cabozantinib (Patients who are otherwise medically eligible for enrollment but have a WBC above 30,000/mm3 are allowed concurrent treatment with hydroxyurea and/or 6-mercaptopurine to stabilize the WBC for up to 15 days of therapy. In these situations, hydroxyurea and/or 6-mercaptopurine will be discontinued once WBC is below 10,000/mm3)
• The subject has laboratory values as follows within 7 days prior to enrollment:
• Bilirubin ≤ 1.5 × the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL
• Serum albumin ≥ 2.8 g/dl
• Serum creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥ 50 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used:
• Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72)
• Female: Multiply above result by 0.85
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN
• Lipase \< 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis
• Urine protein/creatinine ratio (UPCR) ≤ 1
• Serum phosphorus \>2.5, calcium \> 8.4, magnesium \>1.3, and potassium \>3.3. Electrolyte repletion is allowed to reach these values.
• ECOG performance status 0-1.
• LVEF must be equal to or greater than 50%, as measured by MUGA scan or echocardiogram
• Patients, or appropriate designee, must be able to provide informed consent.

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia
• Individuals with a history of other malignancies are ineligible unless:
• They have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy
• Have the following cancers if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
• Subject has uncontrolled intercurrent illness that would limit compliance with study requirements.
• Subject has had prior treatment with cabozantinib
• The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
• The subject has received radiation therapy:
• to the thoracic cavity, abdomen or pelvis within 3 months of the first dose of study treatment or has with ongoing complications or is without complete recovery and healing from prior radiation therapy
• to bone or brain metastasis within 14 days of the first dose of study treatment
• The subject has received any investigational agent within 28 days before the first dose of study treatment.
• The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs.
• The subject has concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment.
• Subjects who are HIV-positive on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with study drug. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Subject carries a diagnosis of active hepatitis B or C.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Exelixis: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Amir Fathi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 8, 2013
• First Posted: October 11, 2013
• Study Start: November 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: January 1, 2017
• Last Updated: July 21, 2017

Record last verified: 2017-07

Locations

US (2)