Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Acute Disease

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Lymphosarcoma

All Drugs and Chemicals

Immunomodulating Agents

Retrospective chart review of children and adults with cancer enrolled on immunotherapy treatment protocols

Nirali N Shah, M.D.

Study Description:

This retrospective protocol focuses on characterizing clinical outcomes and toxicities following CAR T-cell therapy.

Objectives:

Primary

To evaluate the Response Free Survival (RFS) at 6 months following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab

To retrospectively evaluate outcomes following CAR T-cell therapy across children and young adults with B-ALL

Secondary

To evaluate the RFS at 12 months following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab and other immunotherapy.

To evaluate the incidence of CD19 negative versus CD19 positive relapse following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab.

To evaluate the Complete Response (CR) rate following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab.

To evaluate the Minimal Residual Disease (MRD) negative remission rate following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab.

Study Population and Source of Data: Subjects who were less than \< 25 years of age at the time of diagnosis and received a CAR T-cell product for B-ALL.

CAR-Multicenter Analysis (CAR-MA): Retrospective Study to Characterize CAR T-cell Outcomes and Related Toxicities in Children and Young Adults With B-ALL

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

To retrospectively evaluate outcomes following CAR T-cell therapy across children and young adults with B-ALL

To evaluate the RFS at 6 months following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab.

To evaluate the MRD negative remission rate following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab

To evaluate the RFS at 12 months following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab

To evaluate the incidence of CD19 negative versus CD19 positive relapse following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab

To evaluate the CR rate following CD19 CAR stratified by prior blinatumomab vs no prior blinatumomab

National Cancer Institute (NCI)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Cicatrix

Carcinoma

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

Poly(ADP-ribose) Polymerase Inhibitors

Rucaparib

Enzyme Inhibitors

Oral rucaparib

The purpose of this study is to determine which patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib.

Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination (HR) DNA repair deficiency (HRD). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies. An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutations.

Clinical data with PARP inhibitors indicate there is an ovarian cancer patient population beyond just those with germline BRCA (gBRCA) mutations that may benefit from treatment with a PARP inhibitor. This study will define a molecular signature of HRD in ovarian cancer that correlates with response to rucaparib and enables selection of appropriate ovarian cancer patients for treatment with rucaparib. The HRD signature will be based on an association between the extent of genomic scarring (a downstream consequence of HRD) in a patient's tumor and observed clinical benefit from rucaparib treatment. Genomic scarring can be assessed by quantifying the extent of loss of heterozygosity across the tumor genome (tumor genomic LOH). One of the main advantages of detecting tumor genomic LOH is that it can identify HRD tumors regardless of the underlying mechanisms, which include both known (i.e., BRCA mutations) and unknown genetic and other mechanisms.

Once determined, this signature will be prospectively applied to ARIEL2 PART 2 and ARIEL3. This Phase 2 study (ARIEL2) will also compare archival versus recently collected tumor tissue in order to validate the use of archival tumor tissue for assessment of HRD status in ARIEL3.

This study will include 2 parts:

PART 1 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received ≥1 prior platinum-based regimen and had platinum-sensitive disease

PART 2 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens

A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

The primary efficacy endpoint of PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST (Response Evaluation Criteria in Solid Tumors), as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed CR or PR on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or a response per Gynecologic Cancer InterGroup cancer antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. A response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.

Per protocol, the secondary PK endpoint, trough (Cmin) concentrations of rucaparib were summarized with descriptive statistics overall and by cycle in all patients with at least one PK sample collected. Blood samples for trough level PK analysis of rucaparib were drawn at the following timepoints only: on Day 15 of Cycle 1 and on Day 1 of Cycles 2, 3, and 4. Data for other timepoints is not available.

Foundation Medicine

Myriad Genetics, Inc.

pharmaand GmbH

If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.

All patients who participated in Part 1 who received at least one dose of rucaparib

Part 1 Overall

All patients who participated in Part 2 who received at least one dose of rucaparib

Part 2 Overall

Patients with a deleterious BRCA mutation detected in their tumor.

tBRCA

Patients without a BRCA mutation in their tumor, but have high LOH.

Non-tBRCA LOH+

Patients without a BRCA mutation in their tumor, but have low LOH.

Non-tBRCA LOH-

Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).

Non-tBRCA LOH Unknown

Total

Part 1

Part 2

Overall participant count is separated into Part 1 and Part 2 patients.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Number of Prior Chemotherapy Regimens

Number of Prior Platinum Regimens

Refractory = Best response of progressive disease (PD) and PD occurs during or up to 2 months after regimen; Resistant = PD 0-\<6 months after last platinum with best response other than PD; Sensitive = PD ≥6 months after last platinum

Platinum Sensitivity Status

Medical Information Department

Part 1: tBRCA

Part 1: Non-tBRCA LOH+

Part 1: Non-tBRCA LOH-

Part 1: Non-tBRCA LOH Unknown

Safety population by HRD subgroups: Consists of all Part 1 patients who received at least one dose of rucaparib.

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

Part 2: tBRCA

Part 2: Non-tBRCA LOH+

Part 2: Non-tBRCA LOH-

Part 2: Non-tBRCA LOH Unknown

Safety population by HRD subgroups: Consist of all Part 2 patients who received at least one dose of rucaparib.

Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Safety population by HRD subgroups: Consist of all Part 1 patients who received at least one dose of rucaparib

Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

Safety population by HRD subgroups: Consist of all Part 1 and Part 2 patients who received at least one dose of rucaparib.

Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

Efficacy population by HRD subgroups. The overall number of patients analyzed includes only patients with confirmed RECIST CR or PR.

Duration of Response Per RECIST v1.1

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Overall Survival (Part 2 of Study)

Cycle 1 Day 15

Cycle 2 Day 1

Cycle 3 Day 1

Cycle 4 Day 1

All Part 1 and Part 2 patients with at least one PK sample collected

Steady State Trough (Cmin) Level Rucaparib Concentrations

Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor. Part 1 enrolled patients who received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Patients without a BRCA mutation in their tumor, but have high LOH (loss of heterozygosity). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Patients without a BRCA mutation in their tumor, but have low LOH. Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Patients with a deleterious BRCA mutation detected in their tumor. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Patients without a BRCA mutation in their tumor, but have high LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Patients without a BRCA mutation in their tumor, but have low LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Overall Study

Lymphoma, Non-Hodgkin

Analgesics

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Venetoclax

Mitoxantrone

Methotrexate

Ifosfamide

Idarubicin

Isophosphamide mustard

oral bcl-2 inhibitor plus IM2(Ifosfamide plus Mitoxantrone or Idarubicin plus methotrexate) chemotherapy

BCL2 Inhibitor plus IM2 regimen

Xianmin G Song

To evaluate the safety and efficacy of Venetoclax plus IM2 regimen for relapsed and refractory T lymphoblastic lymphoma/leukemia. Dosage of Venetoclax:100mg/d-400mg/d(dose adjustment when concomitant used with CYP3A inhibitor) for 1-28 days (at least 7 days); IM2 regimen: Ifosfamide 1-1.5g/m2/d for 5 days; Mitoxantrone 6-8g/m2/d for 3 days( or Liposome mitoxantrone 20mg/m2 d1 or Idarubicin 6-8mg/m2/d for 3 days) ;methotrexate 1-1.5g/m2/d for 1 day;

Venetoclax Plus IM2 Regimen for Relapsed and Refractory T Lymphoblastic Lymphoma/Leukemia

The Efficacy and Safety of Venetoclax Plus IM2 Regimen for Relapsed and Refractory T Lymphoblastic Lymphoma/Leukemia

complete response rate plus partial response rate

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

principal investigator

Rucaparib 40, 80, 160, 300, 500 mg QD and 240, 360, 480, 600, 840 mg BID, for continuous 21-day cycles. Patients in Part 1 were initially treated in a Dose-escalation Evaluation Period (Cycle 1) and could then continue to receive treatment in an optional Treatment-extension Period (Cycle 2 and beyond).

Rucaparib 600 mg BID for 21-day cycles. Patients also received a single administration of 600 mg rucaparib on both Day -7 and Day 1 for assessing the effect of food on PK.

Oral tablets administered daily with 8 oz (240 mL) of water on an empty stomach or with food; 21-day cycles of treatment. In Part 1, the initial dose level is 40 mg/day (once a day); doses and dosing frequency(e.g. twice a day or three times a day) will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 and Part 3 will receive the RP2D for continuous 21-day treatment cycles until disease progression.

Part 1 (Completed Enrollment) - The purpose of the first part of the study was to evaluate the safety of different doses and dosing regimens of oral rucaparib administered daily to patients with solid tumors.

Part 2A (Completed Enrollment) and Part 2B (Completed Enrollment) - The purpose of the second part of the study is to determine the safety and clinical activity of the RP2D of oral rucaparib administered daily to patients with a known deleterious BRCA mutation (germline or somatic).

Part 3 (Completed Enrollment) - The purpose of the third part of the study is to further evaluate PK of higher dose strength tablets at the RP2D in patients with any advanced solid tumor, inclusive of lymphoma, with evidence of a BRCA mutation (germline or somatic).

Rucaparib (CO-338; formerly known as PF 01367338 and AG 14699) is an orally available, small molecule inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination \[HR\] DNA repair deficiency (HRD). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies.

An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with BRCA1 or BRCA2 mutations. For this study, it is anticipated that rucaparib will promote cell death in the BRCA-deficient tumor cells of ovarian cancer patients with evidence of a germline mutation, thereby limiting tumor progression and providing therapeutic benefit.

A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)

A Phase I/II, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral Rucaparib in Patients With gBRCA Mutation Ovarian Cancer or Other Solid Tumor

The confirmed response rate by RECIST v1.1 is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) on subsequent tumor assessment at least 28 days after first response documentation.

The number of Part 1 (Phase 1) patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.

Cmax = maximum concentration following administration of rucaparib

Tmax = time to maximum concentration following administration of rucaparib

AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation

PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of PD per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan.

Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death, due to any cause. Patients without a documented event of death will be censored on the date of their last visit.

Cmax = maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Cmax values were calculated for each arm.

Tmax = time to maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Tmax values were calculated for each arm.

AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted AUC last values were calculated for each arm.

QTcF value change from baseline by daily dose corrected using Fridericia's method (QTcF). To evaluate the effects of rucaparib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Screening, on Cycle 1 Day -1, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CAR-Multicenter Analysis (CAR-MA): Retrospective Study to Characterize CAR T-cell Outcomes and Related Toxicities in Children and Young Adults With B-ALL	NCT05440409	Leukemia, Acute... Lymphoblastic L...		3 Years - 25 Years	National Institutes of Health Clinical Center (CC)
A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)	NCT01891344	Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Peritoneal Canc...	Oral rucaparib	18 Years -	pharmaand GmbH
Venetoclax Plus IM2 Regimen for Relapsed and Refractory T Lymphoblastic Lymphoma/Leukemia	NCT05576532	T-lymphoblastic... Relapsed Diseas... Refractory Lymp... Refractory Leuk... Safety Efficacy, Self	BCL2 Inhibitor ...	14 Years - 45 Years	Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)	NCT01482715	Ovarian Cancer Fallopian Tube ... Peritoneal Canc... Advanced Solid ...	Rucaparib	18 Years -	pharmaand GmbH
A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)	NCT01891344	Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Peritoneal Canc...	Oral rucaparib	18 Years -	pharmaand GmbH
ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients	NCT02855944	Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Peritoneal Canc...	Chemotherapy Rucaparib	18 Years -	pharmaand GmbH
ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients	NCT02855944	Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Peritoneal Canc...	Chemotherapy Rucaparib	18 Years -	pharmaand GmbH

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