Symptoms and General Pathology

All Conditions

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Heart and Blood Diseases

Rare Diseases

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Lymphoma

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Leukemia, Lymphoid

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Acute Graft Versus Host Disease

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Venetoclax

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Subjects will receive receive short-course venetoclax on day -11 to -6 \[venetoclax 100mg daily administered on day -11 to -6 (total venetoclax dose: 600mg)\], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.

Subjects will receive receive short-course venetoclax on day -11 to -6 \[venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10 to -6 (total venetoclax dose: 1100mg)\], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.

Subjects will receive receive short-course venetoclax on day -11 to -6 \[venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10, 400mg daily administered on day -9 and 600mg daily administered on day -8 to -6 (total venetoclax dose: 2500mg)\], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.

Subjects will receive receive short-course venetoclax on day -11 to -6 \[venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10 and 400mg daily administered on day -9 to -6 (total venetoclax dose: 1900mg)\], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.

Venetoclax is administered as an oral tablet once daily.

Fludarabine is administered as an intravenous infusion at a dose of 30mg/m2 daily, to be administered over 30 minutes.

Cyclophosphamide is administered as an intravenous infusion at a dose of 750mg/m2 daily, to be administered over 30 minutes and to commence 1 hour after fludarabine infusion.

David Ritchie

David Ritchie, MBBS, PhD

Ray Mun Koo, MBBS

Rachel Koldej, PhD

Eric Wong, MBBS, PhD

This is a Phase 1, open-label, single center study of short-course oral venetoclax therapy prior to non-myeloablative conditioning with fludarabine and cyclophosphamide in subjects with haematological malignancies who are planned for allogeneic stem cell transplantation (alloSCT). The primary study objective is to determine the safety and maximum tolerated dose of venetoclax when used in combination with fludarabine and cyclophosphamide conditioning. Secondary objectives were to evaluate the transplant outcomes and donor/recipient engraftment of this regimen.

Eligible patients are to be enrolled sequentially into one of 4 treatment Dose Levels (beginning with Dose Level A) to receive short-course venetoclax on day -11 to -6, followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0. In the dose-escalation phase of this 3+3 study, three patients are planned for each Dose Level.

Dose Level A: venetoclax 100mg daily administered on day -11 to -6 (total venetoclax dose: 600mg)

Dose Level B: venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10 to -6 (total venetoclax dose: 1100mg)

Dose Level C: venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10, 400mg daily administered on day -9 and 600mg daily administered on day -8 to -6 (total venetoclax dose: 2500mg)

Protocol-specific dose-limiting toxicitues (DLTs) will be assessed from the first dose of venetoclax up to day 30 post-transplant. Subjects will not be treated in a new cohort until all subjects in the previous cohort had completed the DLT evaluation period and ≤ 1 of 6 subjects had experienced a DLT. If ≥ 2 of 6 subjects experienced a DLT at Dose Level C, subjects will be treated at Dose B' as part of the dose-escalation phase of this study.

Dose Level B': venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10 and 400mg daily administered on day -9 to -6 (total venetoclax dose: 1900mg)

The maximum tolerated dose (MTD) is defined as the highest Dose Level at which ≤ 1 of 6 subjects had experienced a DLT. The dose-expansion phase involves recruitment of up to 12 patients at the MTD.

Phase 1 study, 3+3 design with dose expansion phase.

Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation

The VICTORY Study: A Phase I Study of Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation

Dose-limiting toxicities (DLT), defined as any of the following which cannot be clearly attributed to a concurrent illness, concomitant medication or those expected as part of standard allogeneic stem cell transplant (alloSCT) complications:

* Any grade 3-4 non-haematological adverse events between day -11 to day -1
* Primary failure of neutrophil engraftment by day 30 post-alloSCT. The date of neutrophil engraftment is defined as the first of 3 consecutive days of neutrophil count ≥ 0.5 x 10\^9/L.
* Primary failure of platelet engraftment by day 30 post-alloSCT. The date of platelet engraftment is defined as the first day of platelet count ≥ 20 x 10\^9/L, with no transfusions for at least 7 days prior.
* Grade 3-4 acute graft-versus-host disease (GVHD) prior to day 30 post-alloSCT
* Development of Clinical Tumour Lysis Syndrome

Acute GVHD (grade 1-4 and grade 3-4) is classified according to the Przepiorka criteria

Chronic GVHD (mild, moderate or severe) is classified according to the Filipovich criteria

GRFS is defined as freedom from grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse or death in the first year following alloSCT

Relapse is defined as recurrence of disease, determined by radiological or histological grounds.

Non-relapse mortality is defined as all-cause mortality without recurrence or progressive disease following alloSCT.

Myeloid and T-cell chimerism by fragment analysis and capillary electrophoresis of shor tandem repeat markers.

Melbourne Health

Behaviors and Mental Disorders

Nervous System Diseases

Neoplasm Metastasis

Attention Deficit Disorder with Hyperactivity

Brain Neoplasms

Acute Disease

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Disease Attributes

Childhood Acute Lymphoblastic Leukemia

Central Nervous System Stimulants

Cardiotonic Agents

Methylphenidate

Dopamine

Dopamine Uptake Inhibitors

Dopamine Agents

Neurotransmitter Agents

Administered 1 capsule each day for 1 week, .3 mg/kg dose.

Administered 1 capsule each day for 1 week.

1 capsule each day for 1 week, .3 mg/kg dose.

Placebo

Alicia Kunin-Batson, Ph.D.

While neurocognitive impairments in attention, memory and executive functioning are commonly reported sequelae of childhood leukemia and brain tumors, studies have only recently begun to examine the treatment of attention deficits in this population. Numerous studies have examined the effectiveness of methylphenidate in the treatment of children with attention deficit hyperactivity disorder (ADHD). However, the effectiveness of this medication for improving attention and behavioral functioning in children with medical illnesses or brain injury are less clear.

Patients will be randomized to receive one week of Metadate CD (a controlled release form of methylphenidate, similar to Ritalin) and one week of placebo in a double-blind fashion.

Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors

Effects of Methylphenidate on Neuropsychological Functioning in Children With Attention Deficits Secondary to Childhood Cancer

Child performance on neuropsychological testing (i.e., using Test of Variables of Attention \[TOVA\] which is a computerized test of attention that assists in the screening, diagnosis, and treatment monitoring of attention disorders, like Attention Deficit Hyperactivity Disorder \[ADHD\], and working memory index of the WisSC IV. Standard scores average = 100 +/- 15. Higher scores indicate better performance. Scores \< or = 1 SD below the mean represent area of deficit.

Parent and teacher ratings of attention, executive function and behavior (i.e., Behavior Rating Inventory of Executive Function \[BRIEF -a parent questionnaire and a teacher questionnaire-designed to assess executive functioning in home and school environments. Conners Parent Rating Scale-3 Short Form \[CPRS-3 research and clinical tool for obtaining parental reports of childhood behavior problems.\] Standard scores average = 50 + or - 10. Higher scores indicate more severe difficulty. Scores \> or = 60 represent areas of significant behavior concern.

Children's Cancer Research Fund United States

University of Minnesota

No patients received treatment, therefore no adverse events were reported.

Participant previously had acute lymphoblastic leukemia or brain tumor to be treated with Methylphenidate or Placebo - Administered 1 capsule each day for 1 week, .3 mg/kg dose.

Participant With Attention Deficit

Age, Categorical

Sex: Female, Male

Only 1 patient was enrolled in this study, no analysis/outcome data can be reported. This patient completed baseline assessment, but withdrew from the study before beginning the medication trial. No medications/placebo were administered.

Alicia Kunin-Batson

No patients received treatment, therefore analysis was not done.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation	NCT05005299	Leukemia, Myelo... Leukemia, Lymph... Leukemia, Lymph... Myelodysplastic... Non-hodgkin Lym... Plasma Cell Mye...	Venetoclax Fludarabine Cyclophosphamid...	18 Years - 75 Years	Melbourne Health
Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors	NCT01100658	ALL, Childhood Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphocytic Leu... Lymphocytic Leu... Lymphocytic Leu... Brain Tumors Cancer of the B... Cancer of Brain Malignant Prima... Brain Neoplasms...	Methylphenidate Placebo	8 Years - 17 Years	University of Minnesota
Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation	NCT05005299	Leukemia, Myelo... Leukemia, Lymph... Leukemia, Lymph... Myelodysplastic... Non-hodgkin Lym... Plasma Cell Mye...	Venetoclax Fludarabine Cyclophosphamid...	18 Years - 75 Years	Melbourne Health
Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors	NCT01100658	ALL, Childhood Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Leukemia, Lymph... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphoblastic L... Lymphocytic Leu... Lymphocytic Leu... Lymphocytic Leu... Brain Tumors Cancer of the B... Cancer of Brain Malignant Prima... Brain Neoplasms...	Methylphenidate Placebo	8 Years - 17 Years	University of Minnesota

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