Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Neoplasms, Second Primary

Liver Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Liver Diseases

Hematinics

All Drugs and Chemicals

Anti-Infective Agents

Liver Extracts

Maraviroc

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

colorectal cancer patients with liver metastases (twelve patients treated with 300 mg/bid)

Niels Halama, MD

Dirk Jaeger, MD

The surface molecule CCR5 is found on tumor cells within liver metastases of colorectal cancer. Inhibition of this molecule leads to a reduction in growth signals for tumor cells and subsequent slowed or halted tumor growth. The agent for the inhibition of CCR5 has already received FDA approval for treatment of HIV and has shown little side effects and toxicities even on long term treatment. Therefore CCR5-inhibition has the potential of providing non-toxic tumor growth inhibition.

CCR5-blockade in Metastatic Colorectal Cancer

Treatment of Advanced Colorectal Cancer Patients With Hepatic Liver Metastases Using the CCR5-Antagonist Maraviroc (Phase I Maracon Trial)

safety, tolerability and feasibility will be assessed after eight weeks of continuous intake of the CCR5-inhibitor. Safety measures include blood analyses (hematologic, liver function, renal function etc.) and the overall performance status of the patient. Especially infections and infection-related events are investigated.

Patients will be evaluated for one year afterwards to assess progression free survival.

Tumor response will be evaluated after eight weeks of continuous treatment with the CCR5-inhibitor, using the RECIST criteria on MRI images (comparing pre- and post-treatment)

The evaluation of tissue alterations within the tumor microenvironment induced by CCR5-inhibition will be performed during the first four weeks of treatment, comparing the pre-treatment tissue situation with the post-treatment situation.

Patients will be evaluated for one year afterwards to assess overall survival.

University Hospital Heidelberg

National Center for Tumor Diseases, Heidelberg

Antineoplastic Agents

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22).

Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22)

Maraviroc will be administered perorally on day 1 to 21 of each cycle (d1-21; qd22)

Dirk Jäger, Prof.

This is a monocentric, single arm, prospective, open-label trial of a combination treatment consisting of pembrolizumab and maraviroc in previously treated subjects who have refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22).

Treatment with pembrolizumab / maraviroc combination will continue until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, administrative reasons requiring cessation of treatment, or completion of treatment per protocol.

Subjects with a treatment response or stable disease after completion of the first treatment phase of eight cycles (core treatment period) will be offered, at the discretion of the investigator, participation in a maintenance phase consisting of up to 24 additional treatment cycles of pembrolizumab monotherapy (total treatment duration up to 24 months).

Subjects who discontinue for reasons other than PD will have post-treatment follow-up for disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed for overall survival (OS) until death, withdrawal of consent, loss to follow-up, or the end of the study.

After the end of treatment, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAEs) and AEs of special interest (AESIs) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.

Combined PD-1 and CCR5 Inhibition for the Treatment of Refractory Microsatellite Stable mCRC

A Phase I Trial of Combined PD-1 Inhibition (Pembrolizumab) and CCR5 Inhibition (Maraviroc) for the Treatment of Refractory Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)

Defined as the rate of patients receiving the protocol treatment according to the planned schedule without occurrence of at least one of the following events:

Study treatment-related Grade ≥ 3 immune-related abnormalities; Study treatment-related Grade ≥ 4 AEs of any aetiology; Any toxic event leading to the premature withdrawal of protocol treatment

The primary safety analysis will be based on subjects who experienced toxicities as defined by the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0; Section 11.2). The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded.

Determine DCR defined as percentage of patients displaying CR/PR or SD as best response according to the RECIST criteria version 1.1.

ORR and immune related (ir) ORR (irORR) will be analyzed.

Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest

Prof. Dr.

Study Treatment Arm

All enrolled subjects received pembrolizumab 200 mg IV on day one every three weeks (d1, qd22; Q3W) plus maraviroc 2 x 300 mg p.o. daily as combination therapy in an unblinded fashion.

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Germany

Region of Enrollment

The required parameters as defined in the inclusion and exclusion criteria are met by all patients.

Dr. Georg Martin Haag

Single Arm, Prospective, Open-label Trial

Feasibility Rate of a Combined Therapy

Safety and Toxicity of a Combined Therapy Based on Subjects Who Experienced Toxicities

Efficacy Endpoint: Disease Control Rate

Efficacy Endpoint: Objective Response Rate

Efficacy Endpoint: Progression-free Survival

Overall Survival

Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22).

Pembrolizumab: Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22)

Maraviroc: Maraviroc will be administered perorally on day 1 to 21 of each cycle (d1-21; qd22)

Overall Study

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Rare Diseases

Sarcoma

Acquired Immunodeficiency Syndrome

HIV Infections

Sarcoma, Kaposi

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Communicable Diseases

Herpesviridae Infections

Virus Diseases

DNA Virus Infections

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Kaposi Sarcoma

Ritonavir

Efavirenz

HIV Protease Inhibitors

Protease Inhibitors

Etravirine

Tipranavir

The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.

FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.

Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.

Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.

Patrick Unemori, MD

Toby Maurer, MD

The purpose of this pilot study is to determine whether Maraviroc is effective in the treatment of Kaposi's Sarcoma (KS), when it does not remit with standard antiretroviral drug therapy.

Although the advent of antiretroviral therapy (ART) may have greatly decreased the incidence of Kaposi's Sarcoma (KS) in resource rich settings, KS continues to be the most prevalent AIDS-defining malignancy in the world and carries with it significant morbidity and mortality. Indeed, in a recent epidemiological study examining cancers in Kampala, Uganda, KS was found to be second only to prostate cancer in terms of incidence rates.

There is growing evidence that C-C chemokine receptor 5 (CCR5) may be involved in the pathogenesis of KS. Kaposi's Sarcoma-associated Herpes Virus (KSHV), an agent found as necessary for KS pathogenesis, encodes viral macrophage inflammatory proteins or vMIP. vMIP-I and vMIP-II have been found to be ligands for chemokine receptors, and in particular the CCR5 receptor \[5, 6\], suggesting a potential role in the inflammatory process needed for KS pathogenesis. Further, vMIP-I induces Ca(2+) mobilization in monocytes expressing CCR5, suggesting an agonistic relationship between vMIP-I and the CCR5 receptor. In addition, vMIP has been found to be proangiogenic when expressed in endothelial cells, a key feature of KS tumor survival. As well, CCR5 has been found to be significantly increased in T cells populations of KS patients (from a preliminary study), and in 2 double-blind, placebo-controlled phase 3 studies in which a total of 1049 patients received the randomly assigned drug MVC, there was a trend revealing a lower incidence of KS in MVC arms vs placebo (0.36% vs 1.43%). This agonistic binding relationship between protein vMIP and CCR5, the proangiogenic activity associated with vMIP, the increased expression of CCR5 in KS, and trend towards lower incidence of KS when patients are taking MVC, suggest CCR5 may play an important role in KS pathogenesis. This involvement of CCR5 in KS pathogenesis implies that MVC may function as a potential therapeutic for KS. To date, there have been no studies examining the effect of MVC on KS.

There is a need for therapeutic development for KS. Standard of care for KS involves initiation or optimization of antiretroviral therapy. A significant proportion of KS cases do not respond to ART alone, with non-response rates ranging from 25-55%, with response times averaging 9 or more months depending on which patient series is identified. In severe or in cases of KS unresponsive to ART, standard of care involves systemic chemotherapy with liposomal doxorubicin, which is not without adverse reactions. Adverse reactions to liposomal doxorubicin include cardiac toxicity, nausea, vomiting, diarrhea, abdominal pain, fatigue, and patients may require pre-regime tests of varying costs, along with resources and time needed for intravenous infusion. Nonresponse rates for liposomal doxorubicin hover around 20%. Focal cases may be more amenable to radiation therapy or intralesional velban. However, radiation and intralesional therapies are limited to focal sites, require monitored visits and specialized care, can be given only in limited amounts, and carry various adverse effects. With these nonresponse rates, potential adverse reactions, and resources and time needed for therapeutic delivery, there are clear benefits proffered by an effective oral therapy requiring minimal monitoring, as is the case with MVC.

Maraviroc (MVC) is a member of a new class of antiretroviral compounds known as small molecule CCR5 antagonists that block R5 HIV entry into cluster of differentiation 4 (CD4) cells. Maraviroc has demonstrated selective and reversible binding to CCR5, as well as potent antiviral activity in vitro against a wide range of laboratory adapted strains of R5 HIV from Clades A, B, C, D, E, F, G, J and O. Maraviroc also retains in vitro antiviral activity against clinical isolates resistant to the existing drug classes, but has no activity against viruses that enter CD4+ cells using CXCR4. In vitro studies with approved antiretroviral medications indicate that there is no evidence of antagonism with any members of the other four classes of antiretroviral medications; nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non- nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) or fusion inhibitors.

Although there is growing evidence that CCR5, a potential therapeutic target, is involved in KS pathogenesis, to date there are no studies examining the effects of a CCR5 inhibitor such as Maraviroc (MVC) on KS. As such, the aim of this study is to examine the effect of Maraviroc, a CCR5 inhibitor, on KS.

Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)

To assess improvements in disease, up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions. The collective surface area of the marker lesions was evaluated over the course of the study for either an increase or decrease in the total surface area of lesions using the modified AIDS Clinical Trials Group (ACTG) Oncology Committee Staging Criteria.

Up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions and the the collective surface area of the marker lesions was evaluated over the course of the study. The percent decrease or increase in the total surface area of lesions was calculated from comparing measurements at baseline and through week 96, or at the last assessment if participant withdrew from the study prior to week 96.

The presence and extent of lower extremity edema was assessed and graded on a scale from 0 to 2 in patients with a higher grade indicating a greater level of edema using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Adverse Events (AE) Grading Table), Version 1.0. Edema grade was recorded at baseline was compared with edema grades recorded at week 96, or at last assessment if participant withdrew from study prior to week 96 and an change in grade was calculated to examine whether or not a decrease in overall grade was observed. A negative value would indicate an overall decrease in the grade of lower extremity edema, and positive value would indicate an overall increase in lower extremity edema.

Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.

Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD4+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD4+ T-Cells

Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD8+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD8+ T-Cells

Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38 positive (DR-CD38+) T-cells

Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38- T-cells

Pfizer

ViiV Healthcare

University of California, San Francisco

No grade 3 or higher adverse events were reported during study. Participants dosage of Maraviroc varied throughout the study depending on their non-interventional anti-viral regimen per FDA recommended dosing guidelines. Dosing was not held or limited based on low-grade adverse events therefore adverse event data was aggregated across all dosages.

The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.

Maraviroc: FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.

Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.

Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.

Treatment Arm (Maraviroc)

Ethnicity (NIH/OMB)

United States

Mean duration of Human Immunodeficiency Virus (HIV) diagnosis

Mean duration of Kaposi's Sarcoma (KS) diagnosis

CD4 is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells

Mean cluster of differentiation 4 (CD4) count

Number of Kaposi's Sarcoma (KS) Lesions at Baseline

Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up. In the remaining eight patients, either the baseline or final follow-up or both specimens had lower than 80% cell viability and were therefore excluded from immunophenotyping analyses. The small sample sizes reduced the statistical power of the reported results.

Dr. Toby Maurer, MD

Number of Participants With a Decrease in Kaposi's Sarcoma (KS) Total Surface Area

Percent Change in KS Total Surface Area

Only seven patients total had measurable edema at any time during the study

Change in Edema Grade

Change in Kaposi's Sarcoma-associated Herpesvirus (KSHV) Viral Load

Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up.

Percent Change in CCR5 Levels on CD4+ T-Cells

Percent Change in CCR5 Levels on CD8+ T-cells

Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Positive (DR-CD38+) T-cells

Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Negative (DR-CD38-) T-cells

Blood and Lymph Conditions

Hematologic Neoplasms

Immunologic Deficiency Syndromes

Graft vs Host Disease

Hematologic Diseases

Homologous Wasting Disease

Antirheumatic Agents

Anti-Inflammatory Agents

Cyclophosphamide

Prednisone

Plerixafor

Bortezomib

Busulfan

Mesna

Pentostatin

RIC+alloHCT+GVHD prophylaxis per dose levels 1, 2, and

Collection of research samples on hematopoietic donors

e-ATG 40 mg/kg/day IV on days -14 and -13. Prednisone tapering doses given orally daily: -days -14 through -12: 1mg/kg/day -days -11 and -10: 0.75 mg/kg/day -days -9 and -9: 050 mg/kg/day -day -7: 0.25 mg/kg/day Pentostatin 4 mg/m2/day IV on days -11 and -7. Cyclophosphamide 5 mg/kg orally or IV daily on days -11 through -4. Busulfan IV AUC targeted dose of 14.8-23.0 mg\*h/L, on days -3 and -2.

Cyclophosphamide 50 mg/kg IV daily Bortezomib 1.3 mg/m2 IV +6 hours and +72 hours after graft infusion Mesna 50 mg/kg IV concomitant with cyclophosphamide

GVHD prophylaxis

allo HCT

In phase 1 dose level 3 and phase 2 only: Plerixafor 240 (Micro)g/kg subcutaneously every other day, starting day +1 through day +21

Phase 1 dose level 2: 300 mg orally twice daily starting day-3 through day day+30

Jennifer A Kanakry, M.D.

Background:

People living with HIV(PLWH) are at a higher risk for cancers that may be curable with a bone marrow transplant. HIV infection itself is no longer a reason to not get a transplant, for patients who otherwise have a standard reason to need transplant.

Objective:

This study is being done to see if a new combination of drugs (cyclophosphamide, maraviroc, and bortezomib) is both safe and effective at protecting against graft-versus-host disease after bone marrow transplant. The study will also test the transplant s impact on your survival and control of your cancer.

Eligibility:

People aged 18 years and older living with HIV and a blood cancer that is eligible for a transplant. Healthy family members aged 12 or older who are half matched to transplant recipients are also needed to donate bone marrow.

Design:

The study will be done in 2 phases. The first phase will be to see if we can safely use a new combination of drugs to prevent GVHD. If the combination is safe in the first phase, the study will proceed to the second phase. In the second phase, we will see if this new combination can better protect against GVHD after transplant.

Participants will be screened. Their diagnoses, organ function and eligibility will be confirmed.

Participants will have a catheter inserted into a vein in their chest or neck. Medications and transfusions will be given through the catheter; blood will be drawn from it.

Participants will be in the hospital for 6 weeks or longer.

They will receive various drugs for 2 weeks to prep their body for the transplant.

The transplant cells will be administered through the catheter.

Participants will continue to receive drug treatments after the transplant.

Blood transfusions may also be needed.

Participants will return 1-2 times per week for follow-up visits for 3 months after discharge.

Participants will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years.

Background:

* Human Immunodeficiency Virus (HIV) infection should not be considered a barrier to hematopoietic cell transplantation (HCT) in patients who otherwise have a standard indication for HCT.
* The main historical barriers include the risk of opportunistic infections, drug interactions, and lack of donor availability.
* This study addresses these barriers by requiring adequate HIV control with anti-retroviral therapies which do not interact with the transplant medications and by utilizing HLA-haploidentical donors.
* Cellular reservoirs that harbor latent HIV are cells of hematopoietic origin, and thus HCT is a potential cure for HIV if all hematopoietic/immune cells can convert to fully donors without HIV infection of these cells.
* CCR5 receptor and CXCR4 are chemokine co-receptors that enable HIV entry into cells.
* Obtaining a CCR5-delta-32 homozygous donor lacks feasibility for the majority of people living with HIV (PLWH) requiring HCT, particularly those of minority ethnic backgrounds.
* Agents used to prevent graft-versus-host disease (GVHD) include post-transplantation cyclophosphamide (PTCy), maraviroc, and bortezomib

  * PTCy expands the donor pool by allowing HLA-mismatched donor HCT with good engraftment and low rates of GVHD. PTCy typically combined with other agents as adjuncts for GVHD prophylaxis, standardly a calcineurin inhibitor and mycophenolate mofetil
  * Bortezomib has been used in combination with PTCy as GVHD prophylaxis and may additionally inhibit HIV infection of donor cells
  * Maraviroc is used as GVHD prophylaxis, but not previously in combination with PTCy and bortezomib, and is additionally a CCR5 receptor blocker, which may inhibit HIV infection of donor cells. Maraviroc is an HIV medication used in modern ART regimens.
  * This protocol is a step-wise evaluation of a GVHD prophylaxis regimen of PTCy and bortezomib in recipients of HLA-haploidentical grafts among those who are on maraviroc, followed by a de-escalation of maraviroc to serve purely as GVHD prophylaxis
* Plerixafor is used in HCT to promote hematopoietic recovery, akin to the use of G-CSF, and is also a CXCR4 blocker, which may inhibit HIV infection of donor cells

Objective:

* To determine a safe and recommended phase II dose level regimen.
* To determine whether a PTCy-based GVHD prophylaxis regimen including maraviroc and bortezomib can maintain adequate protection against grades III-IV acute GVHD (aGVHD), evaluated at day +100.

Eligibility:

* Transplant recipient: age \>= 18 years
* Transplant recipient must be HIV seropositive
* Transplant recipient must have histologically or cytologically confirmed hematologic malignancy with a standard indication for allogeneic HCT, or hematologic malignancy with a standard indication for autologous transplant without access to autologous transplant
* There must be at least one potentially suitable HLA-haploidentical donor.

Design:

* Open-label, single institution, non-randomized, single arm phase II study
* CCR5-delta-32 status will be tested among donor options and homozygous donors will be used, if available
* Conditioning will consist of eATG 40 mg/kg/day IV on days -14 and -13, pentostatin 4 mg/m\^2/day IV on days -11 and -7, low-dose cyclophosphamide 5 mg/kg/day orally daily on days -11 through -4; busulfan IV, pharmacokinetically dosed, on days -3 and -2.
* Bone marrow is the only graft source allowed for this study.
* GVHD prophylaxis will consist of PTCy 50 mg/kg/day IV on days +3 and +4, bortezomib 1.3 mg/m\^2 IV in 2 doses at 6 and 72 hours after graft infusion for all participants. The phase I will include 2 dose levels of de-escalated maraviroc

  * Dose level 1 - PLWH on a maraviroc-containing ART regimen that starts at least 4 weeks before enrollment and continues at least through day +100
  * Dose level 2 - PLWH not on a maraviroc-containing ART regimen, treated with maraviroc 300 mg orally twice daily starting day -3 and given through day +30 purely for GVHD prophylaxis
* If successful completion of dose level 2, dose level 3 will substitute plerixafor in lieu of G-CSF to the dose level 2 regimen. Plerixafor will be given subcutaneously at 240 microgram/kg every other day, beginning at day +1 after transplant through day +21, or longer as clinically indicated, such as until ANC recovery.

Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Bone Marrow Transplantation Followed by Graft-versus-Host-Disease (GVHD) Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies in People Living With HIV

A Phase I/II Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Bone Marrow Transplantation Followed by GVHD Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies in People Living With HIV (PLWH)

.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGAP

Proportion of evaluable recipients who experience grade III-IV acute GVHD at day +100 will be reported along with 80% and 95% two-sided confidence interval

Number and type of toxicities noted for participants who are evaluable

Cumulative incidence of primary and secondary graft failure based on chimerism at day +100 and 1 year post transplant

cumulative incidence of hematopoietic recovery will be based on platelet recover at day +100

Time from transplant to death of any cause and will be determined using the Kaplan-Meier method

Cumulative incidence rates will be estimated based on disease-risk index.

Time from transplant to death from any cause of other event and will be determined using the Kaplan-Meier method

Evaluation by all grades, grade II-IV, and grade III-IV

Evaluation by severity of mild, moderate, and severe

Time from transplant to disease progression and will be determined using the Kaplan-Meier method

cumulative incidence of transplant related mortality will be estimated

National Cancer Institute (NCI)

Syndrome

HIV infected patients in the EuroSIDA cohort who meet the entry criteria for maraviroc pivotal clinical trials (MOTIVATE 1 and MOTIVATE 2)

No intervention is distributed during this trial.

maraviroc

Pfizer CT.gov Call Center

Human Immunodeficiency Virus (HIV) infected patients who meet the entry criteria for the maraviroc pivotal trials (Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients, MOTIVATE) will be identified from the EuroSIDA HIV cohort. The rates of specific clinical adverse events in this identified patient population will be compared with the rates of these events in the participants of the MOTIVATE trials.

All patients in EuroSIDA cohort that meet the entry criteria of MOTIVATE trials are included without any sampling.

EuroSIDA As An External Comparator To MOTIVATE Trials

Incidence And Risk Factors For Acquired Immune Deficiency Syndrome (AIDS) Defining And Non-AIDS Defining Malignancies, And Other AIDS Defining Illnesses In The EuroSIDA Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CCR5-blockade in Metastatic Colorectal Cancer	NCT01736813	Colorectal Canc... Neoplasm Metast... Liver Metastase...	Maraviroc	18 Years -	National Center for Tumor Diseases, Heidelberg
Combined PD-1 and CCR5 Inhibition for the Treatment of Refractory Microsatellite Stable mCRC	NCT03274804	Metastatic Colo... MSS	Pembrolizumab Maraviroc	18 Years -	University Hospital Heidelberg
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)	NCT01276236	Kaposi's Sarcom...	Maraviroc	18 Years -	University of California, San Francisco
Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Bone Marrow Transplantation Followed by Graft-versus-Host-Disease (GVHD) Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies in People Living With HIV	NCT05470491	HIV Hematologic Mal...	RIC GVHD prophylaxi... allo HCT Plerixafor Maraviroc	12 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Combined PD-1 and CCR5 Inhibition for the Treatment of Refractory Microsatellite Stable mCRC	NCT03274804	Metastatic Colo... MSS	Pembrolizumab Maraviroc	18 Years -	University Hospital Heidelberg
Combined PD-1 and CCR5 Inhibition for the Treatment of Refractory Microsatellite Stable mCRC	NCT03274804	Metastatic Colo... MSS	Pembrolizumab Maraviroc	18 Years -	University Hospital Heidelberg
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)	NCT01276236	Kaposi's Sarcom...	Maraviroc	18 Years -	University of California, San Francisco
EuroSIDA As An External Comparator To MOTIVATE Trials	NCT01329783	HIV AIDS	maraviroc	16 Years -	ViiV Healthcare

Spots Global Cancer Trial Database for maraviroc

Every month we try and update this database with for maraviroc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for maraviroc

Every month we try and update this database with for maraviroc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for maraviroc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.