Neoplasms

Blood and Lymph Conditions

All Conditions

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Leukemia

Osteoporosis

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Graft Versus Host Disease

Bone osteodensitometry

Agathe FARGE, PhD

DRCI secretary

MAROLLEAU Jean-Pierre, MD/PhD

Isabelle LEGROUX, PhD

Fabrice JARDIN, MD/PhD

Evaluation of variation of mineral density and bone microarchitecture after allogeneic HSCTs transplant in hematologic malignancies. Comparison with the general population.

Allo-HSCTs performed for the treatment of hematologic malignancies has been increasing in recent years. There is therefore a growing interest in the quality of life of these patients and in particular for the bone complications of the transplant. Indeed, it was found a high incidence of osteoporosis / osteopenia in this population associated with an increased risk of osteoporotic fracture from 6 to 9 times compared to the general population.

This study will evaluate the variation of mineral density and bone microarchitecture parameters by bone densitometry with measurement of trabecular bone score and fracturing risk before and after allogeneic HSCTs transplant, at predefined times. It's also evaluating pain scale, fracture incidence and bone remodeling markers.

Impact of Allo-HSCT on Bone Remodeling: Evolution of Bone Mineral Density and Architecture Measured by Bone Densitometry

Impact of Allo-HSCT on Bone Remodeling: Evolution of Bone Mineral Density and Architecture Measured by Bone Densitometry Coupled With FRAX / TBS in Allo-HSCT

bone mineral density evaluation post-transplant

long term bone mineral density evaluation

evaluation of bone architectural abnormalities and fracture risk

University Hospital, Caen

Symptoms and General Pathology

Acute Disease

Disease Attributes

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Antirheumatic Agents

Micronutrients

Etoposide

Cytarabine

Venetoclax

Mitoxantrone

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Carboplatin

Doxorubicin

Liposomal doxorubicin

Azacitidine

Decitabine

Topotecan

Daunorubicin

Etoposide phosphate

Thioguanine

Asparaginase

Idarubicin

Midostaurin

Sorafenib

Ivosidenib

Clofarabine

Cladribine

Iodine

Cadexomer iodine

Gemtuzumab

Iomab-B in conjunction with a Reduced Intensity Conditioning (RIC) regimen containing Fludarabine and low-dose Total Body Irradiation (TBI) prior to allogeneic HCT

Defined as Investigator's choice of salvage chemotherapy with any combination of the following agents: Azacitidine (not allowed as a single agent), Carboplatin, Cladribine, Clofarabine, Cyclophosphamide, Cytarabine, Daunorubicin, Decitabine (not allowed as a single agent with the exception of patients with documented TP53 mutations who have not previously received 10-day regimens of single agent decitabine), Doxorubicin, Enasidenib, Etoposide, Fludarabine, Gemtuzumab ozogamicin, Idarubicin, Ivosidenib (for subjects with IDH1 mutation), L-Asparaginase, Midostaurin (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Mitoxantrone, Sorafenib (for FLT3 mutant or FLT3-ITD subjects only, not allowed as single agent), Thioguanine, Topotecan, Venetoclax (in combination with a hypomethylating agent). Chemotherapy agents not listed above may be administered after providing clinical justification and receiving medical monitor approval prior to initiation of treatment.

Iomab-B

Conventional Care

Avinash Desai, MD

The primary objective of this study is to demonstrate the efficacy of Iomab-B, in conjunction with a Reduced Intensity Conditioning (RIC) regimen and protocol-specified allogeneic hematopoietic stem cell transplant (HCT), versus Conventional Care in patients with Active, Relapsed or Refractory Acute Myeloid Leukemia (AML).

SIERRA is a pivotal Phase 3 randomized controlled study of Iomab-B in Relapsed or Refractory AML patients. The SIERRA trial has a primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival following randomization to Iomab-B, as well as Event-Free Survival. Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning.

Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia

A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplant Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia (AML)

Defined as CR or CRp lasting 180 days or more from time of initial CR or CRp is documented with evidence of subsequent relapse

Duration of time from randomization to the date of induction treatment failure (ITF), relapse or death

Actinium Pharmaceuticals

Immune System Diseases

Syndrome

Graft vs Host Disease

Preleukemia

Myelodysplastic Syndromes

Recurrence

Bone Marrow Diseases

Precancerous Conditions

Homologous Wasting Disease

Thiotepa

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

After meeting eligibility criteria and being enrolled, patients will receive:

Day -15 to -6 prior to hematopoietic stem cell transplant (HSCT), preparatory regimen of radiation and chemotherapy: Total Myeloid and Lymphoid Irradiation (TMLI): Days -15 to -11 prior to HSCT; - Chemotherapy (infusion): Day -10 to day -6 prior to HSCT: Fludarabine (all days), Thiotepa (days -10 and -9) and Cyclophosphamide and Mesna (days -8 and -7)

Day -4 prior to (HSCT), a Treg-enriched donor cell infusion and graft vs host disease (GVHD) assessment

Day -1 prior to (HSCT), a unmodified donor T Cell infusion and (GVHD) assessment

Day of (day 0) (HSCT), CD34+ Haplo Peripheral Blood Stem Cell Infusion/Transplant and (GVHD) assessment

Days 30, 60,100, 180, 365 post hematopoietic stem cell transplant (HSCT), participants will undergo testing and assessment of minimal residual disease (MRD) and (GVHD)

Total Myeloid and Lymphoid Irradiation (TMLI) delivered through Radiation Oncology institutional standards

Radiation

Given intravenously -10 to -6 days prior to hematopoietic stem cell transplant (HSCT)

Given intravenously on day -10 and day- 9 prior to hematopoietic stem cell transplant (HSCT)

Given intravenously with Mesna on day -8 and day- 7 prior to hematopoietic stem cell transplant (HSCT)

Given intravenously with Cyclophosphamide on day -8 and day -7 prior to hematopoietic stem cell transplant (HSCT)

Given intravenously -4 day prior to hematopoietic stem cell transplant (HSCT)

Treg-enriched donor cell

Given intravenously -1 day prior to hematopoietic stem cell transplant (HSCT)

Unmodified donor T Cell

CD34+ Haplo Peripheral Blood Stem Cell Transplantation

CD34+ Haplo Peripheral Blood Stem Cell

John Koreth, MBBS, DPhil

John Koreth, MD

This research study is evaluating the safety and efficacy of the IS-free Treg-cell graft-engineered haplo transplant method in people with relapsed/refractory and Ultra-high risk acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) receiving a haploidentical donor allogeneic hematopoietic stem cell transplant (HSCT).

The names of the study interventions involved in this study are:

* Radiation-Total Myeloid and Lymphoid Irradiation (TMLI
* Chemotherapy (Fludarabine, Thiotepa, Cyclophosphamide plus Mesna)
* Infusion of haplo Treg-enriched donor cells (experimental therapy)
* Infusion of unmodified haplo donor T cells (includes cancer-fighting T effector cells)
* Infusion of haplo donor CD34+ Peripheral Blood Stem Cells

This study is assessing whether the IS-free Treg-cell graft-engineered haplo HSCT) approach will reduce risk of relapse while preventing usual toxicities related to stem cell transplants (e.g., graft-versus-host-disease (GVHD)). GVHD is a complication of transplantation where the T cells (a type of white blood cell that helps protect the body from relapse by killing cancer cells) in the donor graft attack and damage some of the host tissues. Patients who receive an allogeneic (using another person as the donor) hematopoietic stem cell transplant (HSCT) may develop graft-versus-host disease (GVHD) toxicity and are also at risk of disease relapse.

The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive the study intervention Treg-enriched donor cells and will then be followed for 1 year after transplantation.

It is expected that about 20 people will take part in this research study.

Dana-Farber Cancer Institute research funds along with charitable donations are supporting this research study. Regeneron Pharmaceuticals, Inc. (a pharmaceutical company) is also supporting this research study by providing funding and support for correlative laboratory tests.

IS-free Treg HaploHCT

A Pilot/Phase 1 Study of Immunosuppression-free Regulatory T-cell Graft-engineered Haploidentical Hematopoietic Cell Transplantation in Relapsed/Refractory and Ultra-High-risk AML/MDS

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Safety will be assessed by dose-limiting toxicities (DLT) summarized by patient, type and grade as defined by the CTCAE v5.0.

Will be summarized descriptively and estimated in the competing risks framework treating death without GVHD or without engraftment as a competing event depending on the actual enrolled and evaluable number of patients.

Incidence of grade II-IV and III-IV acute graft vs host disease (GVHD) by day 180 after HCT

Will also be summarized descriptively, estimated in the competing risks framework treating each event as a competing event. Corresponding 95% CIs will be provided.

Estimated using Kaplan-Meier method with exact pointwise confidence intervals

Dana-Farber Cancer Institute

Principal Investigator

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Myeloproliferative Disorders

Leukemia, Biphenotypic, Acute

Leukemia, Lymphoid

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Myeloproliferative Disorders

Acute Leukemia of Ambiguous Lineage

Bendamustine Hydrochloride

Mycophenolic Acid

Tacrolimus

Busulfan

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days; Days -7 through -6: Bendamustine 130 mg/m2 iv x 2 days; Days -5 through -3: Busulfan 1 mg/kg po qid x 3 days; Days +3 through +4: Cyclophosphamide 50 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration

30 mg/m2/day iv x 6 days, days -7 through -2 of HSCT

130 mg/m2 iv x 2 days, Days -7 through -6 of HSCT

1 mg/kg po qid x 3 days, Days -5 through -3

45 mg/kg/day, maximum 3 g/day, iv or po x 30 days, Days +5 through +35

Mycophenolate Mofetil

0.03 mg/kg/day iv or po, Days +5 through +100 with with further correction by concentration. Target concentration 5-15 ng/ml.

Tacrolimus 5Mg Cap

Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning and graft-versus-host disease prophylaxis is associated with high frequency of primary and secondary graft failure. Different technologies of with replete or depleted graft are associated with 10-20% of graft failures. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of disease. Furthermore combination of fludarabine and bendamustine was sufficient to facilitate engraftment in patients with chronic lymphocytic leukemia and lymphomas. The aim of the study is to evaluate whether addition of bendamustine to fladarabine and busulfan conditioning reduces the risk of primary graft failure after haploidentical allograft.

Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)

Request for sharing data with the study plan for the data will be evaluated under common conditions by Pavlov University Ethical Committee.

Proportion of patients with primary and secondary graft failure defined by the absence of donor chimerism

Toxicity assessment is based on NCI CTC AE 5.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Cho et al. criteria. All toxicity measurements will be aggregated as severity scores.

Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease

Cumulative incidence of patients with acute GVHD II-IV grade

Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria.

Cumulative incidence of patients with mortality without hematological relapse of malignancy

Kaplan-Meier estimate of death from all causes

Kaplan-Meier estimate of death or relapse

Cumulative incidence of patients with relapse

St. Petersburg State Pavlov Medical University

Vice-pdirector for science RM Gorbacheva Institute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Chronic Disease

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Days +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration

50 mg/m2 iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation

25 mg/kg iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation

Cyclophosphamid

Ivan S Moiseev, MD, Prof.

Sergey Bondarenko, MD, PhD

Ivan Moiseev

Alexandr Kulagin

Prognosis of patients undergoing salvage allogeneic stem cell transplantation for refractory leukemia or other refractory myeloid malignanies is poor. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. On the other hand post-transplantation cyclophocphamide was reported to abort cytokine release syndrome that sometimes occurs after graft transfusion in patients after haploidentical graft transfusion. The aim of this study is to evaluate if the combination of post-transplantation bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.

Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies

Graft-versus-host Disease Prophylaxis With Combination of Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies (PTBCy)

Measure: Kaplan-Meier estimate of death or relapse, or graft failure

Proportion of patients with cytokine release syndrome according to ASBMT Consensus Grading for Cytokine Release Syndrome, 2018

Toxicity assessment is based on NCI CTC AE 5.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Cho et al.

Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Impact of Allo-HSCT on Bone Remodeling: Evolution of Bone Mineral Density and Architecture Measured by Bone Densitometry	NCT05161026	Myeloid Leukemi...	Bone osteodensi...	18 Years - 75 Years	University Hospital, Caen
Study of Iomab-B vs. Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia	NCT02665065	Acute Myeloid L... Leukemia, Acute... Myeloid Leukemi... Leukemia, Myelo... Acute Myelogeno... Leukemia, Acute... Myelogenous Leu... AML Bone Marrow Tra...	Iomab-B Conventional Ca... HCT	55 Years -	Actinium Pharmaceuticals
IS-free Treg HaploHCT	NCT04678401	Stem Cell Trans... Graft Vs Host D... Myeloid Leukemi... Myeloid Leukemi... Myelodysplastic...	Radiation Fludarabine Thiotepa Cyclophosphamid... Mesna Treg-enriched d... Unmodified dono... CD34+ Haplo Per...	18 Years - 65 Years	Dana-Farber Cancer Institute
IS-free Treg HaploHCT	NCT04678401	Stem Cell Trans... Graft Vs Host D... Myeloid Leukemi... Myeloid Leukemi... Myelodysplastic...	Radiation Fludarabine Thiotepa Cyclophosphamid... Mesna Treg-enriched d... Unmodified dono... CD34+ Haplo Per...	18 Years - 65 Years	Dana-Farber Cancer Institute
Benadamustine, Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation (FluBuBe)	NCT04942730	Leukemia, Acute... Myeloid Leukemi... Biphenotypic Ac... Lymphoblastic L... Myelodysplastic... Myeloproliferat...	Fludarabine Bendamustine Hy... Busulfan Cyclophosphamid... Mycophenolate M... Tacrolimus 5Mg ...	18 Years - 75 Years	St. Petersburg State Pavlov Medical University
IS-free Treg HaploHCT	NCT04678401	Stem Cell Trans... Graft Vs Host D... Myeloid Leukemi... Myeloid Leukemi... Myelodysplastic...	Radiation Fludarabine Thiotepa Cyclophosphamid... Mesna Treg-enriched d... Unmodified dono... CD34+ Haplo Per...	18 Years - 65 Years	Dana-Farber Cancer Institute
Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies	NCT04943757	Myeloid Leukemi... Chronic Myeloid... Myelodysplastic... Myeloproliferat...	Bendamustine Hy... Cyclophosphamid	18 Years - 70 Years	St. Petersburg State Pavlov Medical University

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