Sorafenib Tosylate Before and After Donor Bone Marrow Transplant in Treating Patients With Acute Myeloid Leukemia

NCT01578109 | Completed Phase 1 DMC

• 9 other identifiers: NCI-2012-00727J11116CDR00007306848992P01CA015396P30CA006973P50CA100632U01CA070095UM1CA186691
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 2

Brief Summary

This pilot clinical trial studies the side effects of sorafenib tosylate before and after donor bone marrow transplantation in treating patients with acute myeloid leukemia. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Acute Myeloid Leukemia With FLT3/ITD Mutation

Outcome Measures

Primary Outcomes (1)

• Proportion of patients removed from the study in each cohort due to toxicity

  Will be reported with exact binomial proportions and 95% confidence intervals. All toxicities by type and grade will be reported. The proportion of patients with graft failure in each cohort will also be reported with exact binomial proportions and 95% confidence intervals.

  Up to 24 months

Secondary Outcomes (6)

• Cumulative incidence of non-relapse mortality and relapse

  Up to 2 years

• Disease-free survival (DFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Change in minimal residual disease (MRD)

  Baseline to day 365

• Change in FLT3 suppression

  Baseline to day 365

Other Outcomes (1)

• Changes in T-regulatory cell population

  Baseline to 2 years post-transplant

Study Arms (1)

Treatment (sorafenib tosylate and transplant)

EXPERIMENTAL

Patients receive sorafenib tosylate PO BID beginning at least 30 days after completion of induction therapy and/or transplant and no more than 120 days after transplant continuing for up to 2 years after transplant in the absence of disease progression or unacceptable toxicity.

Procedure: Bone Marrow Transplantation; Drug: Sorafenib; Drug: Sorafenib Tosylate

Interventions

Bone Marrow Transplantation PROCEDURE

Undergo BMT

Also known as: Blood and Bone Marrow Transplant, BMT, Bone Marrow Grafting, Bone Marrow Transplant, Marrow Transplantation

Treatment (sorafenib tosylate and transplant)

Sorafenib DRUG

Given PO

Also known as: BA4 43 9006, BAY 43-9006, Bay-439006

Treatment (sorafenib tosylate and transplant)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Treatment (sorafenib tosylate and transplant)

Eligibility Criteria

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

You may qualify if:

• Acute myeloid leukemia with a FLT3-internal tandem duplication (ITD) who are in a complete remission or partial remission (less than 10% blasts in marrow) as documented by bone marrow biopsy and who plan to undergo a bone marrow transplantation
• Patients who have had count recovery (absolute neutrophil count \[ANC\] \> 500,000/mm\^3; non transfused platelet count over 30,000/mm\^3) and are at least 30 days after induction and/or transplantation but no more than 120 days post transplant
• Patients may have received any prior therapy deemed necessary for induction of remission except for patients whom have progressed while on sorafenib; patients who have responded to sorafenib previously are eligible for enrollment on the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than four months
• Total bilirubin less than 2 x upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional upper limit of normal
• Creatinine =\< 1.5 x upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels \> 1.5 x upper limit of normal
• The effects of sorafenib on the developing human fetus are unknown; for this reason and because tyrosine kinase inhibiting agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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 immediately; contraception should continue for at least 30 days after the last dose of sorafenib
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 2 weeks except for intrathecal chemotherapy (i.e., methotrexate, cytarabine, or thiotepa)
• Patients may not be receiving any other investigational agents
• Patients with uncontrolled hypertension (i.e., persistent grade 3 while undergoing treatment)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
• Patients with active and/or untreated central nervous system (CNS) leukemia will not be eligible
• Patients must not have any evidence of bleeding diathesis or be on any therapeutic anticoagulation such as low molecular weight (LMW) heparin or warfarin for deep vein thrombosis (DVT) treatment
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because sorafenib is chemotherapeutic agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib, breastfeeding should be discontinued if the mother is treated sorafenib
• Human immunodeficiency virus (HIV)-positive patients are excluded because management of these patients in the hematopoietic cell transplant setting has not yet been well defined and is currently the subject of investigation in other studies addressing this issue
• Patients with active acute GVHD who have been initiated on therapy or had therapy escalation within 21 days are not eligible
• Patients with lack of engraftment (less than 90% donor deoxyribonucleic acid \[DNA\] in bone marrow or peripheral blood) after bone marrow transplant as evidence by RFLP (restriction fragment length polymorphism) are not eligible
• Patients who are unable to swallow pills are not eligible
• Patients taking strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors including enzyme-inducing anti-epileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, grape fruit juice, or St. John's wort are not eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Interventions

Bone Marrow Transplantation; Blood Specimen Collection; Sorafenib

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Investigative Techniques; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mark Lewis

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2012
• First Posted: April 16, 2012
• Study Start: January 13, 2012
• Primary Completion: October 28, 2020
• Study Completion: March 7, 2021
• Last Updated: April 2, 2024

Record last verified: 2024-04

Locations

US (2)