A Phase 1/2 interventional study of Crenolanib besylate and Idarubicin in Acute Myeloid Leukemia, sponsored by Arog Pharmaceuticals, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-03.
Sponsored by Arog Pharmaceuticals, Inc. · Phase 1/2, Interventional, and Treatment
This is an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine
For each arm:
The phase I with dose-limiting toxicity (DLT) determination will use 3+3 design.
Phase II total of 52 patients (26 per arm) will be treated at established phase I dose.
Enrollment to be simultaneous to each arm.
3,667 studies on the registry are indexed under Leukemia, Myeloid, Acute; 816 are open to participants now.
This study's enrollment of 28 is below the median of 40 across 3,005 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →Arog Pharmaceuticals, Inc. is the lead sponsor of 17 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Confirmed diagnosis of /relapsed AML or high-risk MDS
Exclusion Criteria:
Arm 1 and 2 Exclusion:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
Drug: Crenolanib besylate · Drug: Idarubicin · Drug: Cytarabine · Drug: Mitoxantrone · Drug: Etoposide · Drug: Fludarabine · Drug: G-CSF
Arm 2 patients will receive crenolanib besylate and azacytidine.
Drug: Crenolanib besylate · Drug: Azacytidine
Also known as: CP-868,596-26
Also known as: 4-demethoxydaunorubicin
Also known as: cytosine arabinoside
Also known as: 5-azacytidine
Also known as: Novantrone
Also known as: etoposide phosphate
Also known as: Fludarabine phosphate
Response Rate of Crenolanib Besylate Combination Therapy
To determine the response rate to crenolanib. CR Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts \<5%, absolute neutrophil count (ANC) \>1×10\^9/L and platelet count \>100×10\^9/L. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS. Death in aplasia response include deaths occurring following chemotherapy while cytopenic with an aplastic or hypoplastic BM prior to death without evidence of persistent leukemia.
Time frame: Baseline up to first documented response, persistent disease, or death (whichever occurs first), 1 year.
| Milestone | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 |
|---|---|---|---|---|---|---|
| Started | 3 | 5 | 12 | 5 | 3 | 0 |
| Completed | 3 | 5 | 10 | 5 | 2 | 0 |
| Not completed | 0 | 0 | 2 | 0 | 1 | 0 |
| Withdrew: Adverse event | 0 | 0 | 1 | 0 | 1 | 0 |
| Withdrew: Physician decision | 0 | 0 | 1 | 0 | 0 | 0 |
To determine the response rate to crenolanib. CR Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts \<5%, absolute neutrophil count (ANC) \>1×10\^9/L and platelet count \>100×10\^9/L. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS. Death in aplasia response include deaths occurring following chemotherapy while cytopenic with an aplastic or hypoplastic BM prior to death without evidence of persistent leukemia.
| Participants | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 |
|---|---|---|---|---|---|---|
| CR/CRi | 2 | 0 | 3 | 1 | 1 | 0 |
| MLFS | 0 | 1 | 1 | 0 | 0 | 0 |
| ORR (CR/CRi+MLFS) | 2 | 1 | 4 | 1 | 1 | 0 |
| Persistent Disease (PD) | 1 | 3 | 7 | 4 | 2 | 0 |
| Death in Aplasia | 0 | 1 | 1 | 0 | 0 | 0 |
Collected over From date of first dose up to 30-days after the last dose, 1 year.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) |
| Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | 5/5 (100%) | 5/5 (100%) | 5/5 (100%) |
| Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | 8/12 (66.7%) | 12/12 (100%) | 12/12 (100%) |
| Crenolanib With 5-azacitidine - Dose Level 1 | 5/5 (100%) | 5/5 (100%) | 5/5 (100%) |
| Crenolanib With 5-azacitidine - Dose Level 2 | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) |
| Crenolanib With 5-azacitidine - Dose Level 3 | — | — | — |
| Event | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 |
|---|---|---|---|---|---|---|
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 0/3 | 1/5 | 0/12 | 2/5 | 0/3 | — |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/3 | 0/5 | 3/12 | 0/5 | 0/3 | — |
| MelaenaGastrointestinal disorders | 0/3 | 0/5 | 0/12 | 0/5 | 1/3 | — |
| Catheter site haemorrhageGeneral disorders | 0/3 | 0/5 | 0/12 | 0/5 | 1/3 | — |
| HyperbilirubinaemiaHepatobiliary disorders | 0/3 | 0/5 | 0/12 | 0/5 | 1/3 | — |
| DiverticulitisInfections and infestations | 0/3 | 0/5 | 0/12 | 0/5 | 1/3 | — |
| Lung infectionInfections and infestations | 0/3 | 0/5 | 2/12 | 0/5 | 1/3 | — |
| PneumoniaInfections and infestations | 1/3 | 1/5 | 0/12 | 1/5 | 0/3 | — |
| Pseudomonas infectionInfections and infestations | 1/3 | 0/5 | 0/12 | 0/5 | 0/3 | — |
| Septic arthritis staphylococcalInfections and infestations | 0/3 | 0/5 | 0/12 | 0/5 | 1/3 | — |
| Event | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 |
|---|---|---|---|---|---|---|
| AnemiaBlood and lymphatic system disorders | 3/3 | 5/5 | 9/12 | 5/5 | 2/3 | — |
| Febrile neutropeniaBlood and lymphatic system disorders | 3/3 | 2/5 | 5/12 | 0/5 | 0/3 | — |
| DiarrhoeaGastrointestinal disorders | 3/3 | 2/5 | 9/12 | 2/5 | 2/3 | — |
| NauseaGastrointestinal disorders | 3/3 | 4/5 | 6/12 | 3/5 | 3/3 | — |
| PyrexiaGeneral disorders | 1/3 | 5/5 | 4/12 | 2/5 | 0/3 | — |
| Blood alkaline phosphatase increasedInvestigations | 3/3 | 2/5 | 3/12 | 3/5 | 1/3 | — |
| HyperglycaemiaMetabolism and nutrition disorders | 3/3 | 4/5 | 7/12 | 3/5 | 2/3 | — |
| HyperphosphataemiaMetabolism and nutrition disorders | 3/3 | 4/5 | 3/12 | 0/5 | 1/3 | — |
| HypoalbunaemiaMetabolism and nutrition disorders | 3/3 | 5/5 | 8/12 | 4/5 | 2/3 | — |
| HypocalcaemiaMetabolism and nutrition disorders | 3/3 | 5/5 | 7/12 | 3/5 | 2/3 | — |
Number of participants analyzed in the arm Crenolanib With 5-azacitidine - Dose Level 3 (100mg Crenolanib) is zero as the study concluded prior to enrolling any participants on this arm.
| Age, Continuous(years) | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 | Total |
|---|---|---|---|---|---|---|---|
| Median | 43 (21 to 67) | 51 (30 to 58) | 65 (19 to 77) | 69 (37 to 81) | 60 (27 to 73) | — | 59.5 (19 to 81) |
| Age, Customized(Participants) | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 | Total |
|---|---|---|---|---|---|---|---|
| 18-60 years | 2 | 5 | 5 | 2 | 2 | 0 | 16 |
| >60 years | 1 | 0 | 7 | 3 | 1 | 0 | 12 |
| Sex: Female, Male(Participants) | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 | Total |
|---|---|---|---|---|---|---|---|
| Female | 1 | 0 | 6 | 4 | 2 | 0 | 13 |
| Male | 2 | 5 | 6 | 1 | 1 | 0 | 15 |
| Race/Ethnicity, Customized(Participants) | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 | Total |
|---|---|---|---|---|---|---|---|
| Black or African American | 1 | 0 | 1 | 0 | 0 | 0 | 2 |
| Asian | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| White | 2 | 4 | 7 | 4 | 2 | 0 | 19 |
| Other | 0 | 1 | 3 | 1 | 1 | 0 | 6 |
| Race/Ethnicity, Customized(Participants) | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 3 | 1 | 0 | 0 | 5 |
| Not Hispanic or Latino | 3 | 4 | 8 | 3 | 3 | 0 | 21 |
| Unknown | 0 | 0 | 1 | 1 | 0 | 0 | 2 |
| FLT3 Mutations(Participants) | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 | Total |
|---|---|---|---|---|---|---|---|
| ITD only | 1 | 1 | 3 | 2 | 3 | 0 | 10 |
| TKD only | 1 | 1 | 5 | 2 | 0 | 0 | 9 |
| ITD and TKD | 1 | 3 | 4 | 1 | 0 | 0 | 9 |
| Baseline ECOG Performance(Participants) | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 | Total |
|---|---|---|---|---|---|---|---|
| 0 | 1 | 1 | 1 | 1 | 0 | 0 | 4 |
| 1 | 2 | 2 | 9 | 3 | 2 | 0 | 18 |
| 2 | 0 | 2 | 2 | 1 | 1 | 0 | 6 |
| Antecedent Hematological Disorder(Participants) | Crenolanib With Standard Salvage Chemotherapy - Dose Level 1 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 2 | Crenolanib With Standard Salvage Chemotherapy - Dose Level 3 | Crenolanib With 5-azacitidine - Dose Level 1 | Crenolanib With 5-azacitidine - Dose Level 2 | Crenolanib With 5-azacitidine - Dose Level 3 | Total |
|---|---|---|---|---|---|---|---|
| Count of participants | 0 | 3 | 4 | 3 | 0 | — | 10 |
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Arog Pharmaceuticals, Inc.