Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Dermatologic Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Dexamethasone

Lenalidomide

Daratumumab

Dexamethasone acetate

BB 1101

Immunoglobulins

Ichthammol

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

INDUCTION: Patients receive carfilzomib IV on days 2, 8, and 15 of cycle 1 and days 1, 8, and 15 of cycles 2-12, lenalidomide PO days 1-21 of each cycle, daratumumab SC days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles, and dexamethasone PO or IV on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive carfilzomib IV on days 1, 8, and 15, lenalidomide PO days 1-21, daratumumab SC day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive carfilzomib IV on day 1, lenalidomide PO days 1-21, daratumumab day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy, MRI and, CT/PET.

Undergo bone marrow aspiration and biopsy

Bone Marrow Aspiration and Biopsy

Carfilzomib

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Clinical Trials Referral Office

Lief Bergsagel, M.D.

Sikander Ailawadhi, M.D.

Clinical Trial Referral Office

Shaji K. Kumar, M.D.

This phase II trial test whether combination chemotherapy works to improve blood test results in patients with high-risk multiple myeloma. Chemotherapy drugs, such as carfilzomib, daratumumab, lenalidomide, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help determine if patients who have a small amount of cancer left after the initial treatment, called minimal residual disease, will benefit from the drug combination.

PRIMARY OBJECTIVE:

I. To estimate the rate of sustained minimal residual disease (MRD) negativity (MRD negative status at any point, with a repeated MRD negative status one year later) in subjects with high-risk multiple myeloma.

SECONDARY OBJECTIVES:

I. To describe the toxicities associated with this treatment approach in subjects with high-risk multiple myeloma (MM).

II. To estimate the overall response rate, very good partial response (VGPR) or better rate and complete response (CR) rate at the end of induction, end of consolidation, end of maintenance and at two years after the completion of treatment.

III. To estimate the progression-free survival and overall survival rate.

CORRELATIVE RESEARCH OBJECTIVES:

I. To describe the clonal architecture through a combination of genomic, epigenomic, proteomic and metabolomic studies before and after treatment, in subjects with high-risk MM.

II. To describe the bone marrow microenvironment through various stages of treatment and the time of MRD negative state and at time of relapse.

OUTLINE:

INDUCTION: Patients receive carfilzomib intravenously (IV) on days 2, 8, and 15 of cycle 1 and days 1, 8, and 15 of cycles 2-12, lenalidomide orally (PO) days 1-21 of each cycle, daratumumab subcutaneously (SC) days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles, and dexamethasone PO or IV on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive carfilzomib IV on days 1, 8, and 15, lenalidomide PO days 1-21, daratumumab SC day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive carfilzomib IV on day 1, lenalidomide PO days 1-21, daratumumab day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy, magnetic resonance imaging (MRI) and, computed tomography/positron emission tomography(CT/PET).

After completion of study treatment, patients are followed up every 6 months for up to10 years.

Combination Treatment Therapy Approaches for the Treatment of High-Risk Multiple Myeloma, REACH Trial

REsponse Adapted Combination Therapy Approaches for High-Risk Multiple Myeloma (REACH)

To determine the clonal architecture before treatment, after treatment in subjects with residual disease and in subjects who have disease progression after attaining MRD negativity.

To evaluate the bone marrow microenvironment before and after treatment and the time of MRD negative state.

MRD negative status at any point, with a repeated MRD negative status one year later). All subjects meeting the eligibility criteria, who have signed a consent form and have begun treatment, will be evaluable, with the exception of subjects determined to be a major violation.

Exact binomial 95% confidence intervals for the true response proportion at each time point will be calculated.

The distribution of overall survival will be estimated using the method of Kaplan-Meier.

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

Adverse Events: All eligible subjects that have initiated treatment will be considered evaluable for assessing adverse event rate(s). The maximum grade for each type of adverse event will be recorded for each subject, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the trial treatment will be taken into consideration. AEs will be summarized overall, as well as by treatment phase (induction, consolidation, maintenance with carfilzomib and lenalidomide and daratumumab).

National Cancer Institute (NCI)

Mayo Clinic

Symptoms and General Pathology

Syndrome

Recurrence

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Neoplasm Metastasis

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Chronic-Phase

Hodgkin Disease

Lymphoma, B-Cell

Leukemia, Biphenotypic, Acute

Leukemia, Myeloid, Accelerated Phase

Lymphoma, Non-Hodgkin

Lymphatic Diseases

Disease Attributes

Bone Marrow Diseases

Precancerous Conditions

Leukemia, B-Cell

Chronic Disease

Myeloproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

B-cell Lymphoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Acute Leukemia of Ambiguous Lineage

Chronic Myeloproliferative Disorders

Antirheumatic Agents

Amino Acids

Tacrolimus

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Melphalan

Mycophenolic Acid

Mechlorethamine

Nitrogen Mustard Compounds

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Calcineurin Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Phenylalanine

Alanine

Patients receive high-dose lenalidomide PO QD on days -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30 minutes on day -4. CD20 positive patients also receive rituximab IV over 6 hours on days -8 to -4.

Patients receive high-dose lenalidomide PO QD on days -7 to -2, cyclophosphamide IV over 3 hours on day -7, and undergo TBI on day -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1.

Undergo allogeneic umbilical cord blood transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Fludarabine Phosphate

Laboratory Biomarker Analysis

Mycophenolate Mofetil

Natural Killer Cell Therapy

Total-Body Irradiation

Umbilical Cord Blood Transplantation

Chitra Hosing

This phase I trial studies the side effects and best way to give natural killer cells and donor umbilical cord blood transplant in treating patients with hematological malignancies. Giving chemotherapy with or without total body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PRIMARY OBJECTIVES:

I. To evaluate the feasibility and safety of ex-vivo expanded cord blood (CB) natural killer (NK) cells with double CB transplantation in patients with hematological malignancies.

SECONDARY OBJECTIVES:

I. To monitor engraftment, chimerism, graft versus host disease, and immune reconstitution in patients receiving expanded CB NK cell therapy.

II. To estimate the time to platelet recovery and the time to absolute neutrophil count (ANC) recovery.

III. To estimate overall survival and disease free survival at one year. IV. To study the in-vivo persistence of cord blood NK cells.

OUTLINE:

PREPARATIVE REGIMEN: Patients are assigned to 1 of 2 treatment plans:

TREATMENT PLAN 1: Patients receive high-dose lenalidomide orally (PO) once daily (QD) on days -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30 minutes on day -4. CD20 positive patients also receive rituximab intravenously (IV) over 6 hours on days -8 to -4.

TREATMENT PLAN 2: Patients receive high-dose lenalidomide PO QD on days -7 to -2, cyclophosphamide IV over 3 hours on day -7, and undergo total body irradiation (TBI) on day -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1.

NK CELL INFUSION: All patients receive ex-vivo expanded cord blood NK cells IV over 30 minutes on day -2.

TRANSPLANT: All patients undergo allogeneic umbilical cord blood transplant on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: All patients receive tacrolimus IV or PO on days -2 to 180 followed by taper and mycophenolate mofetil IV over 2 hours or PO thrice daily (TID) on days -3 to 100.

After completion of study treatment, patients are followed up at 3, 6, and 12 months.

NK Cells in Cord Blood Transplantation

Natural Killer Cells in Allogeneic Cord Blood Transplantation

Will be estimated with 90% credible interval.

The method described by Thall, et al will be used. Will be estimated with 90% credible interval. The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.

Changes from baseline in vital signs and laboratory values will be summarized. Tabulate adverse events by severity and relationship to therapy.

The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.

Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.

M.D. Anderson Cancer Center

Pembrolizumab

Immune Checkpoint Inhibitors

Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab IV over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Patients will receive radiotherapy (8 Gy/1 fx) to an extra-osseous site and/or any bony site containing myeloma deposit.

Radiation Therapy

Mohammad K. Khan, MD, PhD

This pilot clinical trial studies the side effects of pembrolizumab and radiation therapy in treating patients with stage I-III multiple myeloma that has come back after a period of improvement or that does not respond to treatment. Monoclonal antibodies, such as pembrolizumab, may block cancer growth in different ways by targeting certain cells. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving pembrolizumab and radiation therapy may work better in treating patients with stage I-III multiple myeloma.

PRIMARY OBJECTIVE:

I. To evaluate the safety of concurrent single/low dose radiation therapy (radiotherapy) (8 Gy/1fx) in combination with pembrolizumab in relapsed or refractory myeloma patients.

SECONDARY OBJECTIVES:

I. To characterize late toxicity (Common Terminology Criteria for Adverse Events \[CTCAE\] \> grade 2 toxicity at 6 and 12 months) and the effect of radiation in combination with pembrolizumab on systemic response rates using international myeloma working group (IMWG) uniform response criteria for multiple myeloma at 6 months and 12 months.

II. To assess changes in positron emission tomography/computed tomography (PET/CT) as a result of combining pembrolizumab and radiotherapy at 6 months and 12 months.

OUTLINE:

Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.

Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma

Pilot Study of Pembrolizumab and Single-Fraction, Low-Dose, Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma

Greater than grade 2 toxicity will be assessed by Common Terminology Criteria for Adverse Events. Proportion adverse events will be reported.

According to International Myeloma Working Group (IMWG) criteria.

Will be defined using International IMWG criteria.

Will be estimated using the Kaplan-Meier product-limit method.

Merck Sharp & Dohme LLC

National Institutes of Health (NIH)

Emory University

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination Treatment Therapy Approaches for the Treatment of High-Risk Multiple Myeloma, REACH Trial	NCT05497804	ISS Stage III P... Plasma Cell Mye...	Bone Marrow Asp... Carfilzomib Computed Tomogr... Daratumumab Dexamethasone Lenalidomide Magnetic Resona... Positron Emissi...	18 Years - 80 Years	Mayo Clinic
NK Cells in Cord Blood Transplantation	NCT01619761	Accelerated Pha... Acute Biphenoty... Acute Lymphobla... Acute Myeloid L... Chronic Phase C... DS Stage II Pla... DS Stage III Pl... High Grade B-Ce... ISS Stage II Pl... ISS Stage III P... Myelodysplastic... Recurrent Acute... Recurrent Acute... Recurrent Chron... Recurrent Hodgk... Recurrent Non-H... Recurrent Small... Refractory Acut... Refractory Chro... Refractory Hodg... Refractory Non-... Refractory Smal... Secondary Acute... Therapy-Related... Therapy-Related...	Allogeneic Hema... Cyclophosphamid... Fludarabine Pho... Laboratory Biom... Lenalidomide Melphalan Mycophenolate M... Natural Killer ... Rituximab Tacrolimus Total-Body Irra... Umbilical Cord ...	- 75 Years	M.D. Anderson Cancer Center
Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma	NCT03267888	ISS Stage I Pla... ISS Stage II Pl... ISS Stage III P... Recurrent Plasm... Refractory Plas...	Pembrolizumab Radiation Thera...	18 Years -	Emory University

Spots Global Cancer Trial Database for iss stage iii plasma cell myeloma