A Study Evaluating the Safety, Tolerability, Pharmacokinetics and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in Treatment of Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias or Solid Tumors

Phase 2TerminatedNCT04029688

Hoffmann-La Roche38 enrolled

Overview

This is a Phase I/II, multicenter, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of idasanutlin, administered as a single agent or in combination with chemotherapy or venetoclax, in pediatric and young adult participants with acute leukemias or solid tumors. This study is divided into three parts: Part 1 will begin with dose escalation of idasanutlin as a single agent in pediatric participants with relapsed or refractory solid tumors to identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and to characterize dose-limiting toxicities (DLTs). Following MTD/MAD identification, three separate safety run-in cohorts in neuroblastoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) will be conducted to identify the recommended Phase 2 dose (RP2D) of idasanutlin in each combination, with chemotherapy or venetoclax. Part 2 will evaluate the safety and early efficacy of idasanutlin in combination with chemotherapy or venetoclax in newly enrolled pediatric and young adult participants in neuroblastoma, AML,and ALL cohorts at idasanutlin RP2D. Part 3 will potentially be conducted as an additional expansion phase of the idasanutlin combination cohorts in neuroblastoma, AML, or ALL for further response and safety assessment.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia (AML)

Interventions

IdasanutlinDRUG

Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.

VenetoclaxDRUG

Venetoclax will be administered orally at the adult dose equivalent (adjusted by body weight) of 400 milligrams (mg) in participants with neuroblastoma and the adult dose equivalent of 600 mg in participants with leukemia.

CyclophosphamideDRUG

Cyclophosphamide will be administered once daily on Days 1-5 of each 28-day cycle at 250 milligrams per meter squared of body surface area (mg/m\^2) as an intravenous (IV) infusion.

TopotecanDRUG

Topotecan will be administered once daily on Days 1-5 of each 28-day cycle at 0.75 mg/m\^2 as an IV infusion.

FludarabineDRUG

Fludarabine will be administered once daily on Days 1-5 of each 28-day treatment cycle at 30 mg/m\^2 as an IV infusion.

CytarabineDRUG

Cytarabine will be administered once daily on Days 1-5 of each 28-day treatment cycle at 2000 mg/m\^2 as an IV infusion.

Intrathecal ChemotherapyDRUG

All participants with leukemia, irrespective of arm, will receive intrathecal chemotherapy on Day 1 of each 28-day treatment cycle. Intrathecal chemotherapy will consist of either single-agent cytarabine or methotrexate, or a combination of methotrexate, cytarabine, and hydrocortisone, at appropriate age-based dosing as specified in the protocol.

Eligibility

Sex: ALLMin age: 0 YearsMax age: 30 Years

Medical Language ↔ Plain English

Inclusion Criteria: * The participants ages are \< 18 for part 1a, \< 30 for Parts 1b. 2 and 3 * Study Part 1 (single-agent therapy dose escalation): histologically confirmed diagnosis of neuroblastoma or other solid tumor that has progressed or recurred despite standard therapy, and for which there is no therapy proven to prolong survival with an acceptable quality of life * Study Part 1 (combination safety run-in), Study Part 2 (initial expansion), and Study Part 3 (additional expansion): histologically confirmed diagnosis of neuroblastoma, AML, or precursor-B ALL that has progressed or recurred despite, or is refractory to, standard therapy * Adequate performance status: Participants \<16 years of age: Lansky greater than or equal to (≥)50%; Patients ≥16 years of age: Karnofsky ≥50% * Adequate end-organ function, as defined in the protocol * For females of childbearing potential: agreement to remain abstinent, use contraception, agreement to refrain from donating eggs. Females must remain abstinent or use two methods of contraception with a failure rate of \<1% per year during the treatment and follow-up period (variable depending on the combination agent) or in accordance with national prescribing information guidance regarding abstinence, contraception * For males: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, with a female partner of childbearing potential or pregnant female partner, males must remain abstinent or use a condom during the treatment period and for follow-up period (variable, depending on the combination agent) or in accordance with national prescribing information guidance regarding abstinence, contraception Additional Inclusion Criteria for Participants with Solid Tumors (including Neuroblastoma) * At least one evaluable or measurable radiological site of disease as defined by standard criteria for the participant's tumor type, or measurable bone marrow disease by morphology * Adequate hematologic end-organ function, as defined in the protocol * Tumor tissue from relapsed disease Additional Inclusion Criteria for Patients with Leukemia * Bone marrow with ≥5% lymphoblasts by morphologic assessment at screening * Available bone marrow aspirate or biopsy from screening Exclusion Criteria: * Primary Central Nervous System (CNS) tumors * Symptomatic CNS metastases that result in a neurologically unstable clinical state or require increasing doses of corticosteroids or local CNS-directed therapy to control the CNS disease * CNS3 leukemia * Acute promyelocytic leukemia * White blood cell count \>50 × 10\^9 cells/Liter (L) * Down syndrome, Li-Fraumeni syndrome, history of severe aplastic anemia, or any known bone marrow failure predisposition syndrome * Burkitt-type acute lymphoblastic leukemia * T-cell lymphoblastic leukemia * Prior treatment with a MDM2 antagonist * Prior treatment with venetoclax (if potential for enrollment in a venetoclax arm) * Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the participant * Any uncontrolled medical condition or other identified abnormality that precludes the patient's safe participation in and completion of the study * Systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to initiation of study treatment * Treatment with monoclonal antibodies, antibody drug conjugates, or cellular therapy for anti-neoplastic intent within 30 days prior to initiation of study treatment * I-131 meta-iodobenzylguanidine (MIBG) therapy within 6 weeks prior to initiation of study treatment * Myeloablative therapy with autologous or allogeneic hematopoietic stem cell rescue within 100 days of study treatment initiation * Immunosuppressive therapy for treatment of graft-versus-host disease within 2 weeks of study treatment initiation * Radiotherapy within 3 weeks prior to study treatment initiation * Specific restrictions are applicable for patients treated with drugs interacting with CYP2C8, CYP3A4, OATP1B1/B3, and P-gp * Received anti-coagulant or anti-platelet agent within 7 days or 5 half-lives prior to study treatment initiation * Underwent major surgical procedure within 21 days of study treatment initiation, or anticipate need for major surgical procedure during the course of the study

Locations (14)

Arkansas Children's Hospital Research Institute

Little Rock, Arkansas, United States

Lucile Packard Children's Hospital at Stanford University; Thoracic Oncology

Palo Alto, California, United States

Arnold Palmer Hosp-Children

Orlando, Florida, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Alberta Children'S Hospital

Calgary, Alberta, Canada

Centre Leon Berard

Lyon, France

Institut Curie

Paris, France

Prinses Maxima Centrum

Utrecht, Netherlands

Hospital Sant Joan De Deu

Esplugues de Llobregas, Barcelona, Spain

...and 4 more locations

Outcomes

Primary Outcomes

Part 1a and 1b: Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0)

An AE is any untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v5.0. Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to adverse event.

Time frame: From screening up to 30 days after study treatment discontinuation (approximately 7 months)

Parts 1a and 1b: Number of Participants With Dose-Limiting Toxicities (DLTs)

DLTs were assessed for single-agent idasanutlin and idasanutlin in combination with chemotherapy or venetoclax. A DLT was defined as any AE that occurred during the DLT assessment window and was assessed by the investigator as related or possibly related to idasanutlin. An AE is an untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. Following events were considered to be DLTs: any treatment-related death; elevation of serum hepatic transaminase; severe liver injury, in the absence of cholestasis or other causes of hyperbilirubinemia; any non-hematologic toxicity Grade ≥3; nausea, vomiting, and/or diarrhea if Grade 3 severity lasts \> than 24 hours after initiation of supportive care measures or if Grade 4 or higher; hematologic toxicity; any related event that results in a dose delay beyond Day 42.

Time frame: Cycle 1 (one cycle is 28 days)

Part 1b: Objective Response Rate (ORR) in Participants With TP53 Wild-Type (WT) Neuroblastoma Assessed According to International Neuroblastoma Response Criteria (INRC)

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR = \<10 millimeters (mm) residual soft tissue at primary site and complete resolution of meta-iodobenzylguanidine (MIBG) or fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake at primary site. PR = ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR = no tumor infiltration on reassessment.

Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

Parts 2 and 3: ORR in Participants With TP53 WT Neuroblastoma Assessed According to INRC

ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR = \<10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR = ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR = no tumor infiltration on reassessment.

Time frame: Up to approximately 29 months

Parts 2 and 3: Complete Remission Rate (CRR) in Participants With TP53 WT Leukemia

CRR was defined as the percentage of participants with morphologic complete remission (CR), complete remission with incomplete blood count recovery (CRi), or complete remission with incomplete platelet count recovery (CRp) within 2 cycles of study treatment. CR=Bone marrow blasts \<5% (AML) and no evidence of circulating blasts, must be \<1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) \>1.0\*10\^9/liter (L) \[1000/microliter (µL)\]; platelet count \> 100\*10\^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC \<1.0\*10\^9/L\[1000/µL\] or insufficient recovery of platelet count \<100\* 10\^9/L \[100,000/µL\] (AML and ALL). CRp=All CR criteria except for ANC \>1.0\*10\^9/L\[1000/µL\]) or but with insufficient recovery of platelet (\<100\* 10\^9/L \[100,000/µL\]) (ALL).

Time frame: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)

Parts 2 and 3: Minimal Residual Disease (MRD) - Negative Rate in Participants With ALL

MRD - negative rate was defined as percentage of participants with ALL who have an MRD value \< 0.01%, as measured by next-generation sequencing (NGS), within 2 cycles of study treatment.

Time frame: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)

Secondary Outcomes

Part 1a: Clinical Benefit Rate (CBR) in Participants With Solid Tumors From SE Population Assessed According to Response Evaluation Criteria Version 1.1 (RECIST v1.1) or INRC

CBR was defined as the percentage of participants achieving confirmed CR, PR, or stable disease (SD) on 2 consecutive occasions ≥4 weeks apart during the total study period. Per RECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference smallest sum on study. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. CR and PR per INRC were defined as outlined in the description for Part 1b: ORR outcome measure (OM).

Time frame: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)

Part 1b: CBR in Participants With Neuroblastoma From SE Population Assessed According to INRC

CBR=percentage of participants with CR, PR, or SD on 2 consecutive occasions ≥ 4 weeks apart per INRC. Primary tumor: CR=residual soft tissue at primary site is \<10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in longest diameter (LD) of primary site, with stable/improved MIBG/FDG-PET uptake; SD=Insufficient shrinkage for PR/increase for PD. PD= \>20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: CR=resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; SD=no sufficient change in non-primary lesions. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration \>5% or infiltration increased \>2-fold with \>20% tumor infiltration; SD=persistent infiltration at \>5% without meeting other criteria.

Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

Part 1b: CBR in Participants With TP53 WT Neuroblastoma Assessed According to INRC

CBR=percentage of participants with CR, PR, or SD on 2 consecutive occasions ≥ 4 weeks apart per INRC. Primary tumor: CR=residual soft tissue at primary site is \<10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in longest diameter (LD) of primary site, with stable/improved MIBG/FDG-PET uptake; SD=Insufficient shrinkage for PR or increase for PD. PD= \>20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: CR=resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; SD=no sufficient change in non-primary lesions. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration \>5% or infiltration increased \>2-fold with \>20% tumor infiltration; SD=persistent infiltration at \>5% without meeting other criteria.

Part 1a: Duration of Response (DOR) in Participants With Solid Tumors From SE Population Assessed According to RECIST v1.1 or INRC

DOR was defined as the time from the first tumor assessment that supports a participant's objective response (CR or PR) to the time of PD or death from any cause (whichever occurs first), as determined by the investigator using RECIST v1.1 or INRC. Per PRECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. CR/PR/PD were defined per INRC as outlined in the description for the Part 1b: CBR OM.

Time frame: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)

Part 1b: DOR in Participants With Neuroblastoma From SE Population Assessed According to INRC

DOR=time from the first tumor assessment that supports a participant's objective response (CR or PR) to the time of PD or death from any cause (whichever occurs first), as determined by the investigator using INRC for participants with neuroblastoma. Primary tumor: CR=residual soft tissue at primary site is \<10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in LD of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved; PD= \>20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration \>5% or infiltration increased \>2-fold with \>20% tumor infiltration.

Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

Part 1b: DOR in in Participants With TP53 WT Neuroblastoma Assessed According to INRC

Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

Part 1a: Progression Free Survival (PFS) in Participants With Solid Tumors From SE Population Assessed According to RECIST v1.1 or INRC

PFS was defined as the time from initiation of study drug to the first documented occurrence of PD or death from any cause (whichever occurs first), as determined by the investigator using RECIST or INRC. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. PD per INRC: Primary tumor = \>20% increase in LD from smallest sum \& minimum 5 mm increase in LD; Soft tissue \& bone metastases = new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; Bone marrow = new tumor infiltration \>5% or infiltration increased \>2-fold with \>20% tumor infiltration.

Time frame: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)

Part 1a: ORR Irrespective of TP53 Status in Participants With Solid Tumor From SE Population According to RECIST v1.1 or INRC

ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on two consecutive occasions \>= 4 weeks apart, as determined by the investigator according to RECIST v1.1 or INRC. Per RECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. Participants who had neuroblastoma were assessed by INRC. Per INRC, CR= \<10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR= ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR= resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR= no tumor infiltration on reassessment.

Time frame: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)

Part 1b: ORR Irrespective of TP53 Status in Participants With Neuroblastoma From SE Population According to INRC

ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR= \<10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR= ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR= resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR= no tumor infiltration on reassessment. Percentages have been rounded off to nearest decimal point.

Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

Parts 1, 2 and 3: Duration of Objective Response in Participants With Leukemia

DOR, defined as the time from the first tumor assessment that supports the participant's objective response (CR, CRp, CRi) to the time of relapse, or death from any cause, whichever occurs first. CR=Bone marrow blasts \<5% (AML) and no evidence of circulating blasts, must be \<1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) \>1.0\*10\^9/L \[1000µL\]; platelet count \> 100\*10\^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC \<1.0\*10\^9/L\[1000/µL\] or insufficient recovery of platelet count \<100\* 10\^9/L \[100,000/µL\] (AML and ALL). CRp=All CR criteria except for ANC \>1.0\*10\^9/L\[1000/µL\]) or but with insufficient recovery of platelet (\<100\* 10\^9/L \[100,000/µL\]) (ALL). Relapse=participants who achieved a CR/CRp/CRi \& subsequently developed: Bone marrow blasts ≥5%; reappearance of blasts in the blood ≥1%; or development of extra-medullary disease.

Time frame: Up to approximately 29 months

Parts 1, 2 and 3: Event-Free Survival (EFS) in Participants With Leukemia

EFS=time from initiation of study drug to first documented occurrence of M3 marrow after Cycle 1, failure to achieve CR/CRp/CRi after Cycle 2, disease progression, relapse after achieving CR/CRp/CRi, or death from any cause, whichever occurs first. CR=Bone marrow blasts \<5% (AML) \& no evidence of circulating blasts, must be \<1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; ANC \>1.0\*10\^9/L \[1000µL\]; platelet count \> 100\*10\^9/L (100,000/µL); no transfusions for a minimum of 1 week (AML \& ALL). CRi= All CR criteria except for ANC \<1.0\*10\^9/L\[1000/µL\] or insufficient recovery of platelet count \<100\* 10\^9/L \[100,000/µL\] (AML \& ALL). CRp=All CR criteria except for ANC \>1.0\*10\^9/L\[1000/µL\]) or but with insufficient recovery of platelet (\<100\* 10\^9/L \[100,000/µL\]) (ALL). Relapse=participants who achieved a CR/CRp/CRi \& subsequently developed: Bone marrow blasts ≥5%; reappearance of blasts in blood ≥1%; or development of extra-medullary disease.

Time frame: Up to approximately 29 months

Parts 1, 2 and 3: CRR of Efficacy-evaluable Population Irrespective of TP53 Status in Participants With Leukemia

CRR was defined as the percentage of participants with CR, CRi, or CRp within 2 cycles of study treatment. CR=Bone marrow blasts \<5% (AML) and no evidence of circulating blasts, must be \<1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) \>1.0\*10\^9/L \[1000/µL\]; platelet count \> 100\*10\^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC \<1.0\*10\^9/L\[1000/µL\] or insufficient recovery of platelet count \<100\* 10\^9/L \[100,000/µL\] (AML and ALL). CRp=All CR criteria except for ANC \>1.0\*10\^9/L\[1000/µL\]) or but with insufficient recovery of platelet (\<100\* 10\^9/L \[100,000/µL\]) (ALL).

Time frame: Up to approximately 29 months