Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Substance Related Disorders

Behaviors and Mental Disorders

Heart and Blood Diseases

Symptoms and General Pathology

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Drug Overdose

Waldenstrom Macroglobulinemia

Leukemia

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Leukemia, B-Cell

Leukemia, Lymphoid

Chronic Disease

Disease Attributes

B-cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

Indolent B Cell Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Antibodies

Bendamustine Hydrochloride

Rituximab

Vincristine

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

90 mg/m2 I.V. on Day 1 and 2 of each cycle

Bendamustine

Dose per dose escalation protocol, I.V. on Day 2 of each cycle

Vincristine sulfate liposome injection

Adam J Olszewski, MD

This study evaluates addition of Vincristine Sulfate Liposome Injection (Marqibo®) to the standard regimen of Bendamustine and Rituximab in adult patients with indolent B-cell lymphoma. This is a dose-escalation study.

Bendamustine-rituximab is a standard chemotherapy regimen for treatment of many indolent B-cell lymphomas, but most patients experience a recurrence of the lymphoma. Vincristine sulfate has been a traditional component of chemotherapy regimens in non-Hodgkin lymphoma and it is possible that adding it to the bendamustine-rituximab regimen might provide a better quality of remissions or longer duration of remissions with acceptable toxicity.

This is a phase 1, single-center, open-label, single-arm trial in patients with indolent B-cell non-Hodgkin lymphoma otherwise appropriate for bendamustine-rituximab as initial or subsequent line of therapy. Patients will receive the of rituximab and bendamustine in combination with escalating doses of vincristine sulfate liposome injection (Marqibo®). The objective of this study is to assess safety of this combination by establishing the maximum tolerated dose of vincristine sulfate liposome injection (Marqibo®) in the combination.

Vincristine Sulfate Liposome Injection (Marqibo®), Bendamustine and Rituximab-Phase I Trial in Indolent B-cell Lymphoma

BrUOG 326: A Phase I Dose-Escalation Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With Bendamustine and Rituximab (BRiM) in Indolent Non-Hodgkin Lymphoma

Determined as the median of the marginal posterior distribution using data from all available patients

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

The number of patients achieving complete response during treatment on study

Spectrum Pharmaceuticals, Inc

Rhode Island Hospital

The Miriam Hospital

Brown University

Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.

Rituximab: 375 mg/m2 I.V. on Day 1 of each cycle

Bendamustine: 90 mg/m2 I.V. on Day 1 and 2 of each cycle

Vincristine sulfate liposome injection: Dose per dose escalation protocol, I.V. on Day 2 of each cycle

Vincristine Sulfate Liposome Injection: 1.8 mg/m^2

Vincristine Sulfate Liposome Injection: 1.95 mg/m^2

Vincristine Sulfate Liposome Injection: 1.98 mg/m^2

Vincristine Sulfate Liposome Injection: 2.04 mg/m^2

Vincristine Sulfate Liposome Injection: 2.1 mg/m^2

Vincristine Sulfate Liposome Injection: 2.14 mg/m^2

Vincristine Sulfate Liposome Injection: 2.19 mg/m^2

Vincristine Sulfate Liposome Injection: 2.22 mg/m^2

Vincristine Sulfate Liposome Injection: 2.24 mg/m^2

Vincristine Sulfate Liposome Injection: 2.10 mg/m^2

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

BrUOG

Dose-escalation Cohort

Maximum Tolerated Dose

Number of Participants Who Completed Six Cycles of Study Treatment

Response Rate

Vincristine Sulfate Liposome Injection 1.8 mg/m^2

Vincristine Sulfate Liposome Injection 1.95 mg/m^2

Vincristine Sulfate Liposome Injection 1.98 mg/m^2

Vincristine Sulfate Liposome Injection 2.04 mg/m^2

Vincristine Sulfate Liposome Injection 2.10 mg/m^2

Vincristine Sulfate Liposome Injection 2.14 mg/m^2

Vincristine Sulfate Liposome Injection 2.19 mg/m^2

Vincristine Sulfate Liposome Injection 2.22 mg/m^2

Vincristine Sulfate Liposome Injection 2.24 mg/m^2

Complete Response Rate

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Gastrointestinal Agents

Gallium 68 PSMA-11

Androgens

Radiopharmaceuticals

Lactitol

1. Dose Escalation: All eligible participants with mCRPC heavily pre-treated and refractory to 177Lu-labelled PSMA-targeting RLT will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 1.
2. Dose Expansion: Once RDE is determined for Group-1, participants being non/partial responders to 177Lu-labelled PSMA-targeted RLT or requiring re-treatment/re-challenge after 177Lu-labelled PSMA-targeted RLT treatment will be enrolled in Group 1 dose expansion.

1. Dose Escalation: All eligible participants with mCRPC who have received previous treatment with Androgen Receptor Pathway Inhibitors (ARPI) or Computed Tomography (CT) but have never been treated with 177Lu-labelled PSMA-targeted RLT (177Lu-labelled PSMA-targeted RLT treatment naïve) will receive one level higher than the RDE of Group 1 as the starting dose of 225Ac-PSMA-R2 in order to determine the MTD/RDE of Group 2.
2. Dose Expansion: Once RDE is determined for Group 2, participants naïve to 177Lu-labelled PSMA-targeted RLT with high volume soft tissue and visceral disease and in participants with diffuse bone metastasis will be enrolled in Group 2 dose expansion.

Alternatively, if the RDE1 is not determined, Group 2 will begin the evaluation for the dose escalation at the dose of 7 MBq of 225Ac-PSMA-R2 upon Novartis decision. The early starting of Group 2 will be supported by emerging safety and preliminary efficacy data from Group 1 dose escalation.

PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide

225Ac-PSMA-R2

68Ga-PSMA-R2

Novartis Pharmaceuticals

The purpose of the study is to characterize the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of 225Ac-PSMA-R2 in male adult participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with androgen receptor pathway inhibitors in post-177Lu and pre-177Lu settings.

This is an open label, phase I/II, multi-center study which contains two treatment groups (Group 1 and Group 2). Each group has a dose escalation part, once the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) is determined in each of the dose escalation parts, the study will continue with an expansion part in the respective group.

The dose escalation parts will establish the MTD/RDE of the 225Ac-PSMA-R2 guided by the well-established Bayesian Logistic Regression Model (BLRM) method. The adaptive BLRM will be guided by the Escalation with Overdose Control (EWOC) principle to control the risk of DLT in future participants on study. Dose escalation decisions will be performed by the Investigators and Novartis during dose escalation meetings (DEMs) based on safety and tolerability information (BLRM summaries of DLT risk) along with PK and preliminary efficacy information.

The dose expansion parts will assess the anti-tumor activity (Overall Response Rate (ORR) by Prostate Cancer Working Group 3 (PCWG3) modified RECIST 1.1 and Prostate Specific Antigen 50 (PSA50) response rate) as well as further assess the safety, tolerability, and PK of 225Ac-PSMA-R2.

A Phase I/II, Open-label, Multi-center Study of [225Ac]Ac-PSMA-R2 in Men With PSMA-positive Prostate Cancer With or Without Prior 177Lu-PSMA Radioligand Therapy.

SatisfACtion: A Phase I/II, Open-label, Multi-center Study of [225Ac]Ac-PSMA-R2 in Men With Heavily Pre-treated PSMA Positive Metastatic Castration Resistant Prostate Cancer (mCRPC) With or Without Prior 177Lu-labelled PSMA-targeted Radioligand Therapy.

To determine the Recommended Dose for Expansion (RDE) and corresponding regimen for 225Ac-PSMA-R2 monotherapy in PSMA-positive mCRPC in:

* Group-1: Participants previously treated with 177Lu-labelled PSMA-targeted RLT (post-177Lu).
* Group-2: Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu).

The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue, as per BICR and according to Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1, in the absence of bone progression as per PCWG3. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response are first met.

PSA50 response rate is defined as the proportion of participants who have achieved \>= 50% decrease in PSA from baseline confirmed by a second PSA measurement \>= 4 weeks.

Tolerability of study drug will be assessed by summarizing the number of and the reasons for dose delays and dose reductions. Dose intensity will also be tabulated by treatment group.

Disease control rate (DCR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD), as per central and local review and according to PCWG3-modified RECIST v1.1.

Best Overall Response (BOR) is defined to derive Overall Response Rate (ORR) and includes complete response (CR) or partial response (PR). BOR is determined from the sequence of overall responses.

Radiographic progression free survival (rPFS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of radiographic progression as outlined in PCWG3 guideline or death due to any cause.

Overall survival (OS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive (on or before the cut-off date).

Duration of response (DOR) is defined as the time (in months) from the date of the first documented response (CR or PR) to the date of first documented progression according to PCWG3-modified RECIST v1.1 or death due to any cause, among participants with a confirmed response.

Time to a first symptomatic skeletal event (SSE) is defined as the time (in months) from the first administration of 225Ac-PSMA-R2 to the date of SSE or death due to any cause. SSE date is date of the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever comes first.

Biochemical responses as measured by Prostate Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH).

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. T1/2 will be listed and summarized using descriptive statistics.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vincristine Sulfate Liposome Injection (Marqibo®), Bendamustine and Rituximab-Phase I Trial in Indolent B-cell Lymphoma	NCT02257242	Lymphoma, Non-H... Lymphoma, Folli... Lymphoma, Mantl... Lymphoma, Small... Waldenstrom Mac... Lymphoma, B-Cel...	Rituximab Bendamustine Vincristine sul...	18 Years -	Brown University
A Phase I/II, Open-label, Multi-center Study of [225Ac]Ac-PSMA-R2 in Men With PSMA-positive Prostate Cancer With or Without Prior 177Lu-PSMA Radioligand Therapy.	NCT05983198	Metastatic Cast...	225Ac-PSMA-R2 68Ga-PSMA-R2	18 Years -	Novartis
A Phase I/II, Open-label, Multi-center Study of [225Ac]Ac-PSMA-R2 in Men With PSMA-positive Prostate Cancer With or Without Prior 177Lu-PSMA Radioligand Therapy.	NCT05983198	Metastatic Cast...	225Ac-PSMA-R2 68Ga-PSMA-R2	18 Years -	Novartis

Spots Global Cancer Trial Database for escalation with overdose control