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Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia

Primary Purpose

Acute Promyelocytic Leukemia With PML-RARA

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Arsenic Trioxide
Gemtuzumab Ozogamicin
Laboratory Biomarker Analysis
Tretinoin
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Promyelocytic Leukemia With PML-RARA

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • A diagnosis of APL based on the presence of the PML-RAR-alpha fusion gene by cytogenetics, polymerase chain reaction (PCR), or POD test
  • Ability to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of the study
  • Patients in whom therapy for APL was initiated on an emergent basis are eligible (patients may have already started treatment with ATRA, ATO, and/or one dose of idarubicin due to the urgency to start therapy early)
  • Women of child-bearing potential must have a negative serum pregnancy test at screening; in addition to having a negative pregnancy test confirmed at screening, all female participants of childbearing potential must have a negative pregnancy test confirmed within 48 hours prior to dosing with the study drug
  • All sexually active subjects (males and females of child-bearing potential) agree to use 2 effective methods of contraception for the duration of the study

Exclusion Criteria:

  • Fridericia corrected QT (QTcF) interval on the electrocardiogram (EKG) greater than 480 milliseconds
  • Patients with creatinine > 2.5 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease
  • Patients with total bilirubin >= 2.0 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease
  • Patients with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease

Sites / Locations

  • M D Anderson Cancer CenterRecruiting
  • MD Anderson Regional Care Center-KatyRecruiting
  • MD Anderson Regional Care Center-Bay AreaRecruiting
  • MD Anderson Regional Care Center-Sugar LandRecruiting
  • MD Anderson Regional Care Center-The WoodlandsRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)

Arm Description

INDUCTION: Patients receive tretinoin PO BID, arsenic trioxide IV over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4. CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks 1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Event free survival
Monitored using a Bayesian time-to-event model.

Secondary Outcome Measures

Full Information

First Posted
August 2, 2011
Last Updated
October 18, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01409161
Brief Title
Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia
Official Title
Phase II Study of Treatment of Acute Promyelocytic Leukemia (APL) With ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin (GO)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2011 (Actual)
Primary Completion Date
December 18, 2025 (Anticipated)
Study Completion Date
December 18, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial studies how well tretinoin and arsenic trioxide with or without gemtuzumab ozogamicin works in treating patients with previously untreated acute promyelocytic leukemia. Drugs used in chemotherapy, such as tretinoin and arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotoxins, such as gemtuzumab ozogamicin, may find certain cancer cells and kill them without harming normal cells. Giving tretinoin and arsenic trioxide together with gemtuzumab ozogamicin may kill more cancer cells.
Detailed Description
PRIMARY OBJECTIVES: I. Assess whether a combination of all-trans retinoic acid (ATRA [tretinoin]), and arsenic trioxide (ATO) can produce long-term event-free survival in patients with low-risk untreated acute promyelocytic leukemia (APL). II. Assess whether administration of gemtuzumab ozogamicin (GO) at the diagnosis in patients with high-risk APL (white blood cell [WBC] > 10,000) and if the WBC rises to > 10,000 after start of treatment (in patients with low-risk disease) will improve complete response (CR) rate without increasing toxicity in high-risk untreated APL. OUTLINE: INDUCTION: Patients receive tretinoin orally (PO) twice daily (BID), arsenic trioxide intravenously (IV) over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4. CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks 1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Promyelocytic Leukemia With PML-RARA

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
151 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (tretinoin, arsenic trioxide, gemtuzumab ozogamicin)
Arm Type
Experimental
Arm Description
INDUCTION: Patients receive tretinoin PO BID, arsenic trioxide IV over 1-2 hours daily, and gemtuzumab ozogamicin IV over 2 hours once at weeks 1-4. CONSOLIDATION: Patients achieving CR receive arsenic trioxide IV 5 days per week during weeks 1-4, 9-12, 17-20, and 25-28 and tretinoin PO BID for 2 weeks on and 2 weeks off. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Arsenic Trioxide
Other Intervention Name(s)
Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid, Arsenous Acid Anhydride, Arsenous Oxide, Trisenox, White Arsenic
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Gemtuzumab Ozogamicin
Other Intervention Name(s)
Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Tretinoin
Other Intervention Name(s)
2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, Aknoten, all trans-Retinoic acid, All-trans Retinoic Acid, All-trans Vitamin A Acid, all-trans-Retinoic acid, all-trans-Vitamin A acid, ATRA, Avita, beta-Retinoic Acid, Cordes Vas, Dermairol, Epi-Aberel, Eudyna, Renova, Retin-A, Retin-A MICRO, Retin-A-Micro, retinoic acid, Retisol-A, Ro 5488, Stieva-A, Stieva-A Forte, Trans Retinoic Acid, Trans Vitamin A Acid, trans-Retinoic acid, Tretinoinum, Vesanoid, vitamin A acid, Vitamin A acid, all-trans-, Vitinoin
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Event free survival
Description
Monitored using a Bayesian time-to-event model.
Time Frame
The time from the start of treatment to first documentation of disease relapse or death, assessed up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A diagnosis of APL based on the presence of the PML-RAR-alpha fusion gene by cytogenetics, polymerase chain reaction (PCR), or POD test Ability to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of the study Patients in whom therapy for APL was initiated on an emergent basis are eligible (patients may have already started treatment with ATRA, ATO, and/or one dose of idarubicin due to the urgency to start therapy early) Women of child-bearing potential must have a negative serum pregnancy test at screening; in addition to having a negative pregnancy test confirmed at screening, all female participants of childbearing potential must have a negative pregnancy test confirmed within 48 hours prior to dosing with the study drug All sexually active subjects (males and females of child-bearing potential) agree to use 2 effective methods of contraception for the duration of the study Exclusion Criteria: Fridericia corrected QT (QTcF) interval on the electrocardiogram (EKG) greater than 480 milliseconds Patients with creatinine > 2.5 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease Patients with total bilirubin >= 2.0 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease Patients with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Farhad Ravandi-Kashani
Phone
713-745-0394
Email
fravandi@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Phone
713-745-0394
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Facility Name
MD Anderson Regional Care Center-Katy
City
Houston
State/Province
Texas
ZIP/Postal Code
77094
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Phone
713-745-0394
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Facility Name
MD Anderson Regional Care Center-Bay Area
City
Nassau Bay
State/Province
Texas
ZIP/Postal Code
77058
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Phone
713-745-0394
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Facility Name
MD Anderson Regional Care Center-Sugar Land
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77478
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Phone
713-745-0394
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Facility Name
MD Anderson Regional Care Center-The Woodlands
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77384
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani
Phone
713-745-0394
First Name & Middle Initial & Last Name & Degree
Farhad Ravandi-Kashani

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center

Learn more about this trial

Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia

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