Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Neoplasm Metastasis

Neoplastic Processes

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Letrozole

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Patients who were resistant to letrozole will be randomized to receive cyclophosphamide alone or letrozole plus cyclophosphamide. Patients in this arm will receive cyclophosphamide 50 mg daily.

Patients who were resistant to letrozole will be randomized to receive cyclophosphamide alone or letrozole plus cyclophosphamide. Patients in the this will receive cyclophosphamide 50 mg daily plus letrozole 2.5 mg daily.

Patients who haven't received letrozole hormonotherapy will be randomized to receive letrozole plus cyclophosphamide or letrozole alone. Patients in this arm will receive cyclophosphamide 50 mg daily plus letrozole 2.5 mg daily.

Patients who haven't received letrozole hormonotherapy will be randomized to receive letrozole plus cyclophosphamide or letrozole alone. Patients in this arm will receive letrozole 2.5 mg daily.

Cyclophosphamide 50mg

Letrozole 2.5 mg

This is a randomized clinical trial to investigate the efficacy of letrozole combined with metronomic oral cyclophosphamide in elderly metastasis breast cancer patients.

Study in Letrozole Combined With Metronomic Oral Cyclophosphamide in Elderly Metastasis Breast Cancer Patients

Time from the randomization date to the start of disease progression or subject death from any cause (progression assessed by investigator using Response Evaluation Criteria in Solid Tumors 1.1for elderly metastatic breast cancer subjects).

Assessment based on Adverse Events (AEs) , Serious Adverse Events (SAEs), laboratory abnormalities in subjects .

Subjects complete questionnaire in every 8 weeks.

Complete response (CR), Partial response (PR), and Stable Disease (SD) more than or equal to 8 weeks.

Capital Medical University

MD, PhD

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Pathologic Complete Response

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Progression

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Tacrolimus

Etoposide

Fludarabine

Fludarabine phosphate

Methotrexate

Etoposide phosphate

Busulfan

Calcineurin Inhibitors

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Peripheral blood matched related donor HCT, using myeloablative conditioning regimen (IV Busulfan/IV Fludarabine for AML, IV VP16/TBI for ALL) HCT with cyclophosphamide, and oral tacrolimus (or another calcineurin inhibitor if intolerant for tacrolimus) for GVHD prophylaxis. Cyclophosphamide will be given at a dose of 50 mg/kg/day IV on Day +3 and Day +5 post stem cell infusion (only 2 doses).

Peripheral blood matched related donor HCT, using myeloablative conditioning regimen (IV Busulfan/IV Fludarabine for AML, IV VP16/TBI for ALL) HCT with methotrexate, and oral tacrolimus (or another calcineurin inhibitor if intolerant for tacrolimus) for GVHD prophylaxis

Cyclophosphamide as GVHD prophylaxis will be on day +3 and day +5

Methotrexate as GVHD prophylaxis will be on day +1, day +3, and day +6

Riad O El Fakih, MD

Mahmoud D Aljurf, MD, MPH

Marwan Y Shaheen, MD

This randomized clinical trial will evaluate two approaches of GvHD prophylaxis; the standard of care GVHD prophylaxis regimen (methotrexate/calcineurin inhibitors) and post-transplant cyclophosphamide with calcineurin inhibitors for their efficacy as a new GVHD prophylaxis strategy.

An open-label randomized clinical trial will be performed. Eligible patients are females and males, between 14 and 65 years undergoing allo-HCT for treatment of Acute Leukemia (AML or ALL). Patients must have a matching related peripheral blood stem cell donor. Patients from or referred to the KFSH\&RC for allogeneic transplant consideration will be offered the opportunity to participate in this trial.

Treatment Description:

Patients will be randomized on one of the arms; an intervention or a standard of care arm.

Comparing Post-Transplant Cyclophosphamide as GVHD Prophylaxis to Standard of Care for Acute Leukemia Patients

Comparing Post-Transplant Cyclophosphamide With Calcineurin Inhibitors as A GVHD Prophylaxis to Standard Care of Methotrexate and Calcineurin Inhibitors for Acute Leukemia Incorporating Patient Pharmacogenomics Profiling

Defined as the non-occurrence of a grade 3-4 acute GVHD, or systemic therapy-requiring chronic GVHD, or relapse, or death during the first post-transplant year.

The probabilities of grade II-IV and III-IV acute GVHD will be determined. Acute GVHD will be graded according to Glucksberg and NIH 2014 criteria.

The cumulative incidence of systemic therapy-requiring chronic GVHD will be determined. Moderate and severe chronic GVHD will be defined per the NIH 2014 criteria.

King Faisal Specialist Hospital & Research Center

Pembrolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

The treatments received are:

* cyclophosphamide (50 mg/day, daily, per os)
* pembrolizumab (200 mg every 3 weeks, intravenously \[IV\]). On days 1, cyclophosphamide should be taken first and pembrolizumab infusion initiated within 1 hour after cyclophosphamide intake.

One tablet per day. Cyclophosphamide will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

IV infusion every 3 weeks. Pembrolizumab will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Pembrolizumab 100 MG in 4 ML Injection

Olivier TREDAN, MD

The investigators hypothesize that the administration of pembrolizumab combined to metronomic cyclophosphamide may be an interesting therapeutic option for female patients breast cancer with lymphopenia.

Include only patients with breast cancer with lymphopenia is based on the particularly poor prognosis of these patients. The approach suggested here is to deplete and active the immune response of these immunosuppressed patients. The combination of pembrolizumab and cyclophosphamide would provide a higher gain in anti-tumor response in these patients than in those without lymphopenia and in chemotherapy alone.

The investigators proposal is to conduct a multicentric, non-comparative, single arm, two-stage, Phase II trial in lymphopenic patients with metastatic breast cancer.

The study is divided in 2 parts:

* a safety run-in Phase aiming to evaluate the safety of the combination therapy pembrolizumab + metronomic cyclophosphamide based on the occurrence of severe toxicities.
* a two-stage Phase II aiming to evaluate the clinical activity of the combination therapy pembrolizumab + metronomic cyclophosphamide.

In both parts of the study, patients will receive cyclophosphamide (50 mg/day, daily, per os) and pembrolizumab (200 mg every 3 weeks, intravenously \[IV\]). The adverse events of the two drugs are well known.

The initiation of different stage of the study depend on the occurrences of severe toxicities in safety run-in phase and Clinical Benefit rate after 24 weeks in the two-stage Phase II of the study.

Both study drugs will continue to be administered as long as patient experience clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Evaluation of Pembrolizumab in Lymphopenic Metastatic Breast Cancer Patients Treated With Metronomic Cyclophosphamide

CHEMOIMMUNE - A Phase II Study Evaluating an Anti-PD1 Monoclonal Antibody (Pembrolizumab) in Lymphopenic Metastatic Breast Cancer Patients Treated With Metronomic Cyclophosphamide

Number of severe toxicities occurring during the first 6 weeks of treatment and defined as following events evaluated as related to study drugs, using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.03:

* any Grade ≥ 3 non hematological toxicity including in particular events of special interest
* any Grade ≥4 hematological and non-hematological Adverse Event (AE) including.

CBR24w, defined as the percentage of Complete Response (CR), (Partial Response) PR or prolonged Stable Disease (SD) i.e. SD lasting ≥ 24 weeks (pSD) within the evaluable population of patient. Response will be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 and the CBR24w will be summarized by a proportion together with its 95% confidence interval.

The objective response rate (ORR) will be defined as the proportion of patients (described on the efficacy-evaluable population) who achieve complete response (CR) or partial response (PR) as best overall response at 24 weeks of treatment. ORR is based on tumor assessments. Response will be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1

Calculated from date of first documented objective response (i.e., CR or PR) until date of first documented progression disease.

Measured from the date of study drugs start to the date of the first objective disease progression or death.

Defined as the duration of time from start of treatment to time of death.

Adverse Events (AE), vital signs, ECG, physical examination, laboratory safety assessments (hematological and biochemical parameters).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study in Letrozole Combined With Metronomic Oral Cyclophosphamide in Elderly Metastasis Breast Cancer Patients	NCT02583828	Breast Neoplasm... Neoplasm Metast...	Cyclophosphamid... Letrozole 2.5 m...	65 Years -	Capital Medical University
Comparing Post-Transplant Cyclophosphamide as GVHD Prophylaxis to Standard of Care for Acute Leukemia Patients	NCT04314219	Acute Lymphobla... Acute Myeloid L...	Cyclophosphamid... Methotrexate	14 Years - 65 Years	King Faisal Specialist Hospital & Research Center
Study in Letrozole Combined With Metronomic Oral Cyclophosphamide in Elderly Metastasis Breast Cancer Patients	NCT02583828	Breast Neoplasm... Neoplasm Metast...	Cyclophosphamid... Letrozole 2.5 m...	65 Years -	Capital Medical University
Evaluation of Pembrolizumab in Lymphopenic Metastatic Breast Cancer Patients Treated With Metronomic Cyclophosphamide	NCT03139851	Metastatic Brea...	Cyclophosphamid... Pembrolizumab 1...	18 Years -	Centre Leon Berard

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