A Phase 1/2 interventional study of Clofarabine and Idarubicin in Leukemia, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2020-02-24.
Sponsored by M.D. Anderson Cancer Center · Phase 1/2, Interventional, and Treatment
The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can help control Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS). The safety of these study drug combinations will also be studied.
The Study Drugs:
Clofarabine is designed to interfere with the growth and development of cancer cells.
Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells). This may cause the cancer cells to die.
Cytarabine and Fludarabine are designed to insert themselves into the DNA of cancer cells 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 4 groups of 6 participants will be enrolled in the Phase I portion of the study. Up to 280 participants will be enrolled in Phase II.
Phase I:
If you are enrolled in the Phase I portion, the dose of clofarabine you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of clofarabine. Each new group will receive a higher dose of clofarabine than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of clofarabine is found.
All participants will receive the same dose level of idarubicin and cytarabine.
Phase II:
If you are enrolled in the Phase II portion, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups:
Study Drug Administration:
Study drug(s) will be given in what are called "cycles." Each cycle is 28 days.
Phase I:
On Days 1-5:
Phase II (Induction):
The first cycle of study drugs is called Induction. If the doctor thinks it is needed, you will have up to 2 Induction cycles.
If you are in Group 1:
On Days 1-5 of each cycle:
If you are in Group 2:
On Days 1-5 of each cycle:
If the doctor thinks it is needed, you may receive less than 5 days of treatment in the induction cycle.
If the doctor thinks it is needed, your dose level will be reduced after Induction.
Phase II (Consolidation):
If the disease responds to the study drugs, you may receive up to 6 more cycles of study drugs. This is called Consolidation.
If you are in Group 1:
On Days 1-3 of each cycle :
If you are in Group 2:
On Days 1-3 of each cycle:
If the cancer does not completely respond after Cycle 1, you may repeat induction (Cycle 1). If the cancer completely responds, you will begin the consolidation cycles.
If the doctor thinks it is needed, you may receive less than 3 days of treatment in the consolidation cycles.
Study Visits:
You will have a physical exam, including measurement of your vital signs before the start of each cycle. Blood (about 2 teaspoons) will be drawn for routine tests every 3-7 days.
On Day 28 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 Study:
You may continue taking the study drugs for as long as the doctor thinks it is in your best interest or up to 8 total cycles. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.
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 you are off study, you will be called and asked 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. Cytarabine and Idarubicin are FDA approved and commercially available for the treatment of AML. Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Clofarabine is FDA approved and commercially available for the treatment of acute lymphoblastic leukemia (ALL). The combination of these study drugs is investigational.
Up to 292 patients will take part in Phase I and Phase II of this study. All will be enrolled at MD Anderson.
5,441 studies on the registry are indexed under Leukemia; 637 are open to participants now.
This study's enrollment of 282 is above the median of 38 across 4,248 interventional studies indexed under Leukemia.
Browse Leukemia studies →M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.
Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.
Drug: Clofarabine · Drug: Idarubicin · Drug: Cytarabine · Drug: Fludarabine
Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine Maximum Tolerated Dose (MTD) based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
Drug: Clofarabine · Drug: Idarubicin · Drug: Cytarabine
Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.
Drug: Idarubicin · Drug: Cytarabine · Drug: Fludarabine
Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle.
Also known as: Clofarex, Clolar
10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.
Also known as: Idamycin
1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.
Also known as: Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride
30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).
Also known as: Fludara
Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine
MTD is highest dose level in which \<2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities.
Time frame: 28 days
Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI)
NCI \& Myelodysplastic syndromes (MDS) International Working Group (IWG) Definitions: Complete Response (CR): Neutrophil count ≥1.0 ×10\^9/L, Platelet count ≥100 ×10\^9/L, Bone marrow aspirate \</=5% blasts, No extramedullary leukemia; CRi: Response as in CR but platelets \<100 ×10\^9/L; Partial response (PR): Neutrophil count ≥ 1.0 ×10\^9/L, Platelet count ≥100 ×10\^9/L, ≥ 50% reduction in bone marrow blasts over baseline; Clinical benefit: In addition to IWG criteria, in AML, a decrease in bone marrow blasts to \<5% is also considered clinical benefit; Stable Disease: In addition to IWG criteria and in absence any of above response criteria, stable disease considered if the bone marrow blast percent does not increase compared to pretreatment level; Relapse: Increase of bone marrow blasts to \>10% after initial response. Response assessed Day 28 of every 2-3 cycles during treatment.
Time frame: 12 months
Event-Free Survival (EFS) at 2 Years
Comparison of the event-free survival (EFS) between treatment CIA and FLAI, where an event is defined to be resistance to treatment, relapse (after response) or death, whichever occurred first.
Time frame: Up to 2 years or until relapse/death
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up.
Time frame: up to 2 years
| Milestone | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI |
|---|---|---|---|
| Started | 12 | 157 | 113 |
| Completed | 12 | 157 | 113 |
| Not completed | 0 | 0 | 0 |
MTD is highest dose level in which \<2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities.
| mg/m^2 | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI |
|---|---|---|---|
| Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine | 15 | — | — |
NCI \& Myelodysplastic syndromes (MDS) International Working Group (IWG) Definitions: Complete Response (CR): Neutrophil count ≥1.0 ×10\^9/L, Platelet count ≥100 ×10\^9/L, Bone marrow aspirate \</=5% blasts, No extramedullary leukemia; CRi: Response as in CR but platelets \<100 ×10\^9/L; Partial response (PR): Neutrophil count ≥ 1.0 ×10\^9/L, Platelet count ≥100 ×10\^9/L, ≥ 50% reduction in bone marrow blasts over baseline; Clinical benefit: In addition to IWG criteria, in AML, a decrease in bone marrow blasts to \<5% is also considered clinical benefit; Stable Disease: In addition to IWG criteria and in absence any of above response criteria, stable disease considered if the bone marrow blast percent does not increase compared to pretreatment level; Relapse: Increase of bone marrow blasts to \>10% after initial response. Response assessed Day 28 of every 2-3 cycles during treatment.
| Participants | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI |
|---|---|---|---|
| Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) | — | 107 | 76 |
Comparison of the event-free survival (EFS) between treatment CIA and FLAI, where an event is defined to be resistance to treatment, relapse (after response) or death, whichever occurred first.
| Months | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI |
|---|---|---|---|
| Event-Free Survival (EFS) at 2 Years | — | 7.1 (1 to 69) | 8.4 (1 to 69) |
Time from date of treatment start until date of death due to any cause or last Follow-up.
| Months | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI |
|---|---|---|---|
| Overall Survival | — | 14.5 (1 to 70) | 15.1 (1 to 70) |
Collected over up to 1 year. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Clofarabine + Idarubicin + Cytarabine | 4/12 (33.3%) | 10/12 (83.3%) | 12/12 (100%) |
| Group 1 CIA | 8/157 (5.1%) | 126/157 (80.3%) | 150/157 (95.5%) |
| Group 2 FLAI | 5/113 (4.4%) | 89/113 (78.8%) | 109/113 (96.5%) |
| Event | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI |
|---|---|---|---|
| InfectionGeneral disorders | 7/12 | 52/157 | 23/113 |
| Neutropenic FeverInfections and infestations | 2/12 | 75/157 | 57/113 |
| DeathGeneral disorders | 4/12 | 5/157 | 2/113 |
| PainGeneral disorders | 0/12 | 12/157 | 12/113 |
| ColitisGastrointestinal disorders | 1/12 | 0/157 | 2/113 |
| Hand Foot SyndromeSkin and subcutaneous tissue disorders | 1/12 | 0/157 | 0/113 |
| HyperbilirubinemiaMetabolism and nutrition disorders | 1/12 | 1/157 | 0/113 |
| Nausea/VomitingGastrointestinal disorders | 1/12 | 5/157 | 5/113 |
| HemorrhageBlood and lymphatic system disorders | 0/12 | 6/157 | 8/113 |
| Deep Vein ThrombosisVascular disorders | 0/12 | 3/157 | 3/113 |
| Event | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI |
|---|---|---|---|
| InfectionInfections and infestations | 11/12 | 70/157 | 39/113 |
| Neutropenic FeverInfections and infestations | 8/12 | 94/157 | 48/113 |
| Rash/DesquamationSkin and subcutaneous tissue disorders | 7/12 | 40/157 | 11/113 |
| HyperbilirubinemiaMetabolism and nutrition disorders | 1/12 | 43/157 | 14/113 |
| PainGeneral disorders | 0/12 | 43/157 | 24/113 |
| NauseaGastrointestinal disorders | 1/12 | 42/157 | 27/113 |
| Elevated Alanine AminotransferaseMetabolism and nutrition disorders | 2/12 | 40/157 | 11/113 |
| FatigueGeneral disorders | 1/12 | 29/157 | 21/113 |
| DiarrheaGastrointestinal disorders | 2/12 | 29/157 | 20/113 |
| Elevated Aspartate AminotransferaseMetabolism and nutrition disorders | 2/12 | 17/157 | 4/113 |
| Age, Categorical(Participants) | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 11 | 153 | 108 | 272 |
| >=65 years | 1 | 4 | 5 | 10 |
| Age, Continuous(years) | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI | Total |
|---|---|---|---|---|
| Median | 52 (27 to 68) | 53 (20 to 68) | 51 (18 to 69) | 53 (18 to 69) |
| Sex: Female, Male(Participants) | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI | Total |
|---|---|---|---|---|
| Female | 6 | 74 | 55 | 135 |
| Male | 6 | 83 | 58 | 147 |
| Race (NIH/OMB)(Participants) | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 1 | 6 | 6 | 13 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 3 | 20 | 11 | 34 |
| White | 8 | 122 | 85 | 215 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 9 | 11 | 20 |
| Region of Enrollment(participants) | Clofarabine + Idarubicin + Cytarabine | Group 1 CIA | Group 2 FLAI | Total |
|---|---|---|---|---|
| United States | 12 | 157 | 113 | 282 |
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