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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2013-00548 | Registry Identifier | NCI CTRP |
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The goal of Phase I of this clinical research study is find the highest tolerable dose of clofarabine that can be given with decitabine, idarubicin, and cytarabine to patients with acute leukemia.
The goal of Phase II of this study is to learn if decitabine followed by the combination of clofarabine, idarubicin, and cytarabine can help to control acute leukemia. The safety of this drug combination will also be studied.
Decitabine and idarubicin are designed to damage the DNA (the genetic material of cells). This may cause cancer cells to die.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Cytarabine is designed to insert itself into DNA and stop the DNA from repairing itself.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 3 groups of 6 participants will be enrolled in the Phase I portion of the study. Up to 74 participants will be enrolled in Phase II.
Phase I:
If you are enrolled in the Phase I portion, the number of days of clofarabine you receive will depend on when you joined this study. The first group of participants will receive clofarabine for 4 days. Each new group will receive clofarabine for the same number of days, if no intolerable side effects were seen. The number of days may be reduced to 3. The clofarabine dose per day is the same from group to group.
All participants will receive the same dose level of decitabine, idarubicin and cytarabine.
Phase II:
If you are enrolled in the Phase II portion, you will receive decitabine, idarubicin, and cytarabine. You will receive clofarabine for the highest number of days that was tolerated in the Phase I portion.
All participants will receive the same dose level of decitabine, idarubicin, cytarabine, and clofarabine.
Study Drug Administration:
Each study drug cycle is 33 days. The first cycle of study drugs is called Induction. If the doctor thinks it is needed, you will have up to 2 Induction cycles.
Phase I (Induction):
On Days 1-5 of each cycle, you will receive decitabine 1 time a day by vein over about 1 hour.
On Days 6-10 of each cycle:
If the doctor thinks it is needed, your dose level will be reduced after Induction.
If the doctor thinks it is needed, you may receive fewer days of treatment in the Induction cycle(s).
Phase II (Induction):
On Days 1-5 of each cycle, you will receive decitabine 1 time a day by vein over about 1 hour.
On Days 6-10 of each cycle:
If the doctor thinks it is needed, your dose level will be reduced after Induction.
If the doctor thinks it is needed, you may receive fewer days of treatment in the Induction cycle(s).
Phases I and II (Consolidation):
If the disease responds to the study drugs, you may receive up to 6 more study drug cycles. This is called Consolidation.
On Days 1-5 of each cycle:
°You will receive decitabine 1 time a day by vein over 1 hour.
On Days 6-8 of each cycle:
If the doctor thinks it is needed, you may receive fewer days of treatment in the Consolidation cycles.
Study Visits:
Before the start of each cycle, you will have a physical exam, including measurement of your vital signs.
Every 3-7 days, blood (about 2 teaspoons) will be drawn for routine tests.
On Day 33 of every 2-3 cycles (+/- 7 days), if the doctor thinks it is needed, you will have a bone marrow aspirate to check the status of the disease. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
Length of Treatment:
You may continue taking the study drugs for up to 8 cycles. 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.
Your participation on the study will be over once you have completed the long-term follow-up.
Long-term Follow-up:
Every 3 months for 1 year after your last study drug dose, the study staff will call you and ask how you are feeling, about any side effects you may be having, and about any other drugs you may be taking. These calls should last about 5 minutes each.
This is an investigational study. Decitabine is FDA approved and commercially available to treat myelodysplastic syndrome (MDS). Clofarabine is FDA approved and commercially available to treat ALL in children. Idarubicin and cytarabine are FDA approved and commercially available to treat AML. The study drug combination is investigational.
Up to 92 participants will be enrolled in this study. All will take part at MD Anderson.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clofarabine + Cytarabine + Decitabine + Idarubicin | Experimental | Phase I - Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10) Phase II - Clofarabine 15 mg/m2 by vein over approximately 1 hour daily (number of days selected based on Phase I portion). Decitabine 20 mg/m2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m2 by vein over approximately 2 hours daily for 5 days (days 6-10) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Decitabine | Drug | Phase I and II - 20 mg/m2 by vein daily for 5 days (days 1-5) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Clofarabine | Maximum tolerated dose (MTD) defined as the highest dose schedule in which 6 patients were treated with at most 1 experiencing a dose-limiting toxicity (DLT). Clofarabine 15 mg/m2 IV over approximately 1 hour daily (number of days selected based on Phase I portion). | After second, 33 day cycle |
| Number of Participants With a Response | Primary endpoint is overall response defined as the best response either complete response, complete remission without platelet recovery, or complete remission without incomplete blood count recovery within 56 days. | 56 days |
| Measure | Description | Time Frame |
|---|---|---|
| To Determine the Disease-free Survival (DFS). | Time from date of treatment start until the date of first objective documentation of return of disease. | Up to 2 years after participants off study date |
| Overall Survival |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nitin Jain, MBBS | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| University of Texas MD Anderson Cancer Center Website | View source |
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All participants in the phase I portion of the study received dose level 1 of the study medication. None of the participants experienced a DLT as defined in the protocol.
Period 1: Dose level 1 - Clofarabine 15mg/m^2 daily x 4 days (days 6-9) Period 2: Dose level-1 - Clofarabine 15mg/m^2 daily x 3 days (days 6-8)
Recruitment Period: 1/2013 to 01/2018
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| ID | Title | Description |
|---|---|---|
| FG000 | Period 1 | Phase I Clofarabine + Cytarabine + Decitabine + Idarubicin Phase I - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Clofarabine: Phase I Starting Dose - 15 mg/m^2 by vein daily for 4 days (days 6-9) |
| FG001 | Period 2 | Phase I Clofarabine + Cytarabine + Decitabine + Idarubicin Phase I - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Clofarabine: Phase I Dose level -1 - 15 mg/m^2 by vein daily for 3 days (days 6-9) |
| FG002 | Phase II Clofarabine + Cytarabine + Decitabine + Idarubicin | Phase II - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Phase II - Clofarabine 15 mg/m^2 by vein over approximately 1 hour for 4 days (days 6-9). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All participants in the phase I portion of the study received dose level 1 of the study medication. None of the participants experienced a DLT as defined in the protocol.
Period 1 Dose level 1 - Clofarabine 15mg/m^2 daily x 4 days (days 6-9) Period 2 Dose level-1 - Clofarabine 15mg/m^2 daily x 3 days (days 6-8)
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| ID | Title | Description |
|---|---|---|
| BG000 | Period 1 | Phase I Clofarabine + Cytarabine + Decitabine + Idarubicin Phase I - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Clofarabine: Phase I Starting Dose - 15 mg/m^2 by vein daily for 4 days (days 6-9) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) of Clofarabine | Maximum tolerated dose (MTD) defined as the highest dose schedule in which 6 patients were treated with at most 1 experiencing a dose-limiting toxicity (DLT). Clofarabine 15 mg/m2 IV over approximately 1 hour daily (number of days selected based on Phase I portion). | All participants in the phase I portion of the study received dose level 1 of the study medication. None of the participants experienced a DLT as defined in the protocol. Period 1: Dose level 1 - Clofarabine 15mg/m^2 daily x 4 days (days 6-9) Period 2: Dose level-1 - Clofarabine 15mg/m^2 daily x 3 days (days 6-8) | Posted | Number | mg/m^2 x 4 days (6-9) | After second, 33 day cycle |
|
3 years
All participants in the phase I portion of the study received dose level 1 of the study medication. None of the participants experienced a DLT as defined in the protocol.
Period 1 Dose level 1 - Clofarabine 15mg/m^2 daily x 4 days (days 6-9) Period 2 Dose level-1 - Clofarabine 15mg/m^2 daily x 3 days (days 6-8)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Period 1 | Phase I Clofarabine + Cytarabine + Decitabine + Idarubicin Phase I - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Clofarabine: Phase I Starting Dose - 15 mg/m^2 by vein daily for 4 days (days 6-9) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Kidney Injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nitin Jain, MD./Associate Professor | The University of Texas MD Anderson Cancer Center | 713-745-6080 | njain@mdanderson.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 2, 2014 | Apr 15, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000077209 | Decitabine |
| D015255 | Idarubicin |
| D003561 | Cytarabine |
| D000077866 | Clofarabine |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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Starting with Dose level 1, the participants were enrolled by cohort of 3. Once the DLT assessment is completed, another cohort of 3 patients will be enrolled. If at any time, we see more than 30% patients experiencing DLT, we will de-escalate to dose level (-1).
Period 1: Dose level 1 Clofarabine 15mg/m^2 daily x 4 days (days 6-9)
Period 2: Dose level-1 Clofarabine 15mg/m^2 daily x 3 days (days 6-8)
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| Idarubicin | Drug | Phase I and II - 10 mg/m2 by vein daily for 3 days (days 6-8) |
|
|
| Cytarabine | Drug | Phase I and II - 1 g/m2 by vein daily for 5 days (days 6-10) |
|
|
| Clofarabine | Drug | Phase I Starting Dose - 15 mg/m2 by vein daily for 4 days (days 6-9) Phase II Starting Dose - Maximum tolerated dose from Phase I (number of days selected based on Phase I portion). |
|
|
Time from date of treatment start until date of death due to any cause or last Follow-up.
| Up to 2 years after participants off study date |
| BG001 | Period 2 | Phase I Clofarabine + Cytarabine + Decitabine + Idarubicin Phase I - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Clofarabine: Phase I Dose -1 - 15 mg/m^2 by vein daily for 3 days (days 6-9) |
| BG002 | Phase II Clofarabine + Cytarabine + Decitabine + Idarubicin | Phase II - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Phase II - Clofarabine 15 mg/m2 by vein over approximately 1 hour for 4 days (days 6-9). |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Period 2 | Clofarabine + Cytarabine + Decitabine + Idarubicin Phase I - Decitabine 20 mg/m^2 by vein over approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein over approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein over approximately 2 hours daily for 5 days (days 6-10) Clofarabine 15 mg/m^2 by vein over approximately 1 hour daily |
|
|
| Primary | Number of Participants With a Response | Primary endpoint is overall response defined as the best response either complete response, complete remission without platelet recovery, or complete remission without incomplete blood count recovery within 56 days. | One of the 47 participants on the Phase II portion of this study who received study medication was not evaluable for response. | Posted | Count of Participants | Participants | 56 days |
|
|
|
| Secondary | To Determine the Disease-free Survival (DFS). | Time from date of treatment start until the date of first objective documentation of return of disease. | One of the 47 participants on the Phase II portion of this study who received study medication was not evaluable for response. | Posted | Median | Full Range | months | Up to 2 years after participants off study date |
|
|
|
| Secondary | Overall Survival | Time from date of treatment start until date of death due to any cause or last Follow-up. | One of the 47 participants on the Phase II portion of this study who received study medication was not evaluable for response. | Posted | Median | Full Range | Months | Up to 2 years after participants off study date |
|
|
|
| 1 |
| 18 |
| 18 |
| 18 |
| 17 |
| 18 |
| EG001 | Period 2 | Phase I Clofarabine + Cytarabine + Decitabine + Idarubicin Phase I - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Clofarabine: Phase I Dose level -1 - 15 mg/m^2 by vein daily for 3 days (days 6-9) | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | Phase II Clofarabine + Cytarabine + Decitabine + Idarubicin | Phase II - Decitabine 20 mg/m^2 by vein for approximately 1 hour daily for 5 days (days 1-5) Idarubicin 10 mg/m^2 by vein for approximately 30 minutes daily for 3 days (days 6-8) Cytarabine 1 g/m^2 by vein for approximately 2 hours daily for 5 days (days 6-10) Phase II - Clofarabine 15 mg/m2 by vein over approximately 1 hour for 4 days (days 6-9). | 5 | 46 | 33 | 46 | 27 | 46 |
| Death | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Elevated Transaminases | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastric Hemorrhage | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperbilirubinemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Left Ventricular Failure | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neutropenic Fever | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Seizures | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Septic Shock | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Abcess | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Bronchopulmonary Hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Intracranial Hemorrhage | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neutropenia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Typhlitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperbilirubinemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Elevated Transaminases | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D007951 | Leukemia, Myeloid |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D001087 | Arabinonucleosides |
| D000227 | Adenine Nucleotides |
| D011685 | Purine Nucleotides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D009711 | Nucleotides |
| D012265 | Ribonucleotides |