Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Blinatumomab

Blinatumomab as continuous intravenous infusion at dose of 28 µg/24 hours over 4 weeks followed by 2 week treatment-free period for 6-week treatment cycle; 4 cycles of blinatumomab at 3, 6, 9, and 12 months following hematopoietic cell transplantation (HCT).

Participants receive Blinatumomab as continuous intravenous infusion at a dose of 28 µg/24 hours over 4 weeks followed by a treatment-free period of 2 weeks, defined as one 6-week treatment cycle. In the first induction cycle, the initial dose of Blinatumomab is 9 µg/day for the first 7 days of treatment which then will be escalated (dose step) to 28 µg/day starting on day 8 (week 2) through day 29 (week 4). For all subsequent cycles, 28 µg/day is the dose for all 4 weeks of continuous treatment. Participants receive 4 cycles of blinatumomab at 3, 6, 9, and 12 months following hematopoietic cell transplantation (HCT).

Hematopoietic Cell Transplantation

Partow Kebriaei, MD

You are being asked to take part in this study because you either had Ph positive B-lineage acute lymphoblastic leukemia (ALL) or still have a small amount of the disease and recently received an allogeneic stem cell transplant (cells from someone else).

The goal of this clinical research study is to learn if blinatumomab in patients who have had an allogeneic stem cell transplant can help to control ALL or prevent ALL from coming back in patients who either have a small amount of ALL or have had ALL in the past. The safety of this drug will also be studied.

Study Drug Administration:

Every study cycle will be 6 weeks. You may receive up to 4 cycles of blinatumomab. Each cycle will start around 3, 6, 9, and 12 months after your stem cell transplant.

In each cycle, you will receive blinatumomab as a continuous infusion by vein for 4 weeks, followed by a 2 week "rest period" during which you will not receive blinatumomab.

You will need to remain in the hospital for the first 2 cycles so that you can be checked on for side effects.

Length of Study:

You may receive blinatumomab for up to 1 year. You will no longer be able to receive the study drug if the disease comes back (if you do not have ALL), if the disease gets worse (if you have a small amount of ALL), if intolerable side effects occur, or if you are unable to follow study directions.

Study Visits:

Before each cycle:

* You will have a physical exam. As part of the physical exam, you will be checked for graft versus host disease (GVHD, when transplanted donor tissue attacks the tissues of the recipient's body).
* Blood (about 4 tablespoons) will be drawn to learn the effectiveness of the stem cell transplant.
* You will have a bone marrow biopsy and aspiration to check the status of the disease and for cytogenetic testing.

Once a week during each cycle, blood (about 4 tablespoons) will be drawn for routine tests.

End of Study Visit:

About 2 weeks after your last dose of blinatumomab:

* You will have a physical exam.
* Blood (about 4 tablespoons) will be drawn to learn the effectiveness of the stem cell transplant.
* You will have a bone marrow biopsy and aspiration to check the status of the disease and for cytogenetic testing.

This is an investigational study. Blinatumomab is FDA approved and commercially available for the treatment of Philadelphia chromosome (Ph) negative B-ALL that has returned after treatment. Its use in patients with Ph positive B-lineage ALL is investigational.

Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.

Blinatumomab Maintenance Following Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Lymphoblastic Leukemia

Participants with treatment-related toxicities attributable to Blinatumomab. Toxicities defined as any 1) grade 3-4 acute GVHD greater than 30%, 2) secondary graft failure \>30%, or 3) nonrelapse mortality (NRM) within one cycle of Blinatumomab.

Number of participants with progression free survival from the date of allogeneic HCT to the date of disease progression or death. (Progression is defined as more than 5% blast in the peripheral blood or bone marrow biopsy.)

Number of participants in the study who are alive and disease free up to 1 year.

Amgen

M.D. Anderson Cancer Center

Blinatumomab as continuous intravenous infusion at dose of 28 µg/24 hours over 4 weeks followed by 2 week treatment-free period for 6-week treatment cycle; 4 cycles of blinatumomab at 3, 6, 9, and 12 months following hematopoietic cell transplantation (HCT).

Blinatumomab: Participants receive Blinatumomab as continuous intravenous infusion at a dose of 28 µg/24 hours over 4 weeks followed by a treatment-free period of 2 weeks, defined as one 6-week treatment cycle. In the first induction cycle, the initial dose of Blinatumomab is 9 µg/day for the first 7 days of treatment which then will be escalated (dose step) to 28 µg/day starting on day 8 (week 2) through day 29 (week 4). For all subsequent cycles, 28 µg/day is the dose for all 4 weeks of continuous treatment. Participants receive 4 cycles of blinatumomab at 3, 6, 9, and 12 months following hematopoietic cell transplantation (HCT).

Hematopoietic Cell Transplantation: Hematopoietic progenitor cell infusion

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Mexico

Region of Enrollment

Partow Kebriaei, MD / Stem Cell Transplantation Department

Number of Participants With Toxicities

Progression Free Survival (PFS)

Overall Survival (OS)

Overall Study

Daratumumab

Participants receive Daratumumab by vein over about 4 hours on Days 1, 8, 15, and 22 of Cycles 1 and 2, Days 1 and 15 of Cycles 3-6, and then on Day 1 of Cycles 7 and beyond.

Each cycle is 28 days.

16 mg/kg by vein weekly for the first 2 cycles (8 weeks) of treatment, followed by every 2 weeks for 4 cycles (or 16 weeks) and then every 4 weeks until progression or up to 1 year of treatment whichever comes earlier.

Gautam Borthakur, MBBS

The goal of this clinical research study is to learn if daratumumab can help to control B- or T-cell acute lymphoblastic leukemia (ALL). The safety of daratumumab will also be studied.

This is an investigational study. Daratumumab is FDA approved and commercially available for treatment of multiple myeloma. It is considered investigational to use daratumumab to treat ALL.

The study doctor can explain how the study drug is designed to work.

Up to 72 participants will be enrolled in this study. All will take part at MD Anderson.

Study Drug Administration:

Each cycle is 28 days.

If you are found to be eligible to take part in this study, you will receive daratumumab by vein over about 4 hours on Days 1, 8, 15, and 22 of Cycles 1 and 2, Days 1 and 15 of Cycles 3-6, and then on Day 1 of Cycles 7 and beyond. Your first dose of daratumumab will be given over about 7 hours.

In this study, the following will be done to lower the chance of a daratumumab infusion related reaction:

* You will get medications, including steroids, acetaminophen, and/or antihistamine before the infusion. If you are considered high risk, you may also get medications, including inhaled steroids, after the infusion.
* The infusion may be slowed down or stopped if you have a reaction.
* You may stay overnight in the hospital after the infusion so the study staff can check your health.

You may ask the study staff for information about how these drugs are given and their risks. You may also be asked to stay in the hospital overnight to watch you for side effects, if needed.

Length of Study:

You may receive daratumumab for up to 1 year. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Study Visits:

Within 24 hours before your first dose of study drug, if you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test.

Every 2 weeks during Cycles 1-6, blood (about 1 teaspoon) will be drawn for CMV testing.

On Day 1 of Cycles 1 and 2:

* You will have a physical exam.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* During Cycle 2, you will have a bone marrow aspirate/biopsy to check the status of the disease.

On Days 8, 15, 22 of Cycles 1 and 2, blood (about 2 teaspoons) will be drawn for routine tests.

On Day 1 of Cycles 3-6:

* You will have a physical exam.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* During Cycle 3, you will have an EKG.
* If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test.

On Day 1 of Cycles 3 and beyond, you will have a bone marrow biopsy/aspirate to check the status of the disease. If the disease appears to be responding to the study drug, the study doctor will decide how often you will have this procedure.

On Day 15 of Cycles 3-6, blood (about 2 teaspoons) will be drawn for routine tests.

On Day 1 of Cycles 7 and beyond:

* You will have a physical exam.
* Blood (about 2 teaspoons) will be drawn for routine tests and CMV testing.
* During Cycle 7 only, you will have an EKG.
* If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test.

End of Treatment:

About 28-35 days after the last dose of daratumumab:

* You will have a physical exam.
* You will have an EKG.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* If the doctor thinks it is needed, you may have a bone marrow biopsy/aspiration to check the status of the disease.

Follow-Up Visits:

The study staff will call you to ask how you are doing 1 time each month for the first year after your End-of-Treatment visit, then every 6 months during the second year after the visit, and then 1 time every year after that. Each call should last about 5 minutes.

At 30 and 60 days after your last dose of study drug and then every 2-3 months after that for 1 year:

* You will have a physical exam.
* If the disease appeared to be responding to the study drug, blood (about 2 teaspoons) will be drawn for routine tests. Every 4-12 weeks, this sample may be used for CMV testing. If the disease appears to get worse, you will stop having these blood draws.
* If the disease appeared to be responding to the study drug, you will have a bone marrow aspirate and/or biopsy.
* If the disease appeared to be responding to the study drug, you will have an EKG at your first follow-up visit.

After 1 year, you may continue to have follow-up visits as part of your routine care. This will be discussed with you by the study doctor in more detail.

Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory B-cell or T-cell Precursor Acute Lymphoblastic Leukemia (ALL)

An Open-label Phase 2 Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory B-cell or T-cell Precursor Acute Lymphoblastic Leukemia (ALL)

Overall response (OR) defined as achievement of complete remission (CR), CR with only Partial Hematological Recovery (CRp), Complete Response without Hematological Recovery (CRi).

Descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 utilized for adverse event reporting.

Janssen Scientific Affairs, LLC

Symptoms and General Pathology

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Amino Acids

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants take Ibrutinib capsules by mouth every day for 3, 28 day cycles.

During Cycle 1, participants receive the highest dose of Ibrutinib by taking 3 capsules each day. During Cycle 2, participants receive the second-highest dose and will take 2 capsules each day. During Cycle 3, participant takes the lowest dose of Ibrutinib and takes 1 capsule each day.

Cycle 1 daily dose of ibrutinib is 420 mg (3 capsules), in the second cycle 280 mg (2 capsules), and in the third cycle 140 mg (1 capsule).

Prithviraj Bose, MD

Ibrutinib is currently FDA approved and commercially available for the treatment of CLL. However, some researchers think the approved dose may be unnecessarily high.

The goal of this clinical research study is to compare 3 different daily doses of ibrutinib to learn how these doses affect the disease and your body. Researchers think that if a lower dose of ibrutinib can be found to be as effective as the currently approved dose this may help to lower the risk of side effects.

Study Drug Administration:

Each study cycle is 28 days.

If you are found to be eligible to take part in this study, you will take ibrutinib capsules by mouth every day for 3 cycles. Each dose of ibrutinib should be taken at about the same time, either with or without food.

During Cycle 1, you will receive the highest dose of ibrutinib (the dose that is currently FDA approved). You will take 3 capsules each day during Cycle 1. During Cycle 2, you will receive the second-highest dose and you will take 2 capsules each day. During Cycle 3, you will take the lowest dose of ibrutinib and you will take 1 capsule each day.

You must swallow the ibrutinib capsules whole without opening, breaking, or chewing them.

You will be given a study drug diary to keep track of each dose of ibrutinib taken, including the time the dose was taken, any missed or vomited doses and the reason for missing the dose, and any doses that you vomited.

Study Visits:

On Days 1, 8 and 28 of each cycle blood (about 1-2 tablespoons total) will be drawn before your dose of ibrutinib and then at 4 and 24 hours after your dose for pharmacodynamic (PD) and pharmacokinetic (PK) testing, to help researchers understand how ibrutinib works in the body, and to learn if the dose you are taking is as effective as other doses (Exception: there will be no 4-hour blood draw on day 28). PK testing measures the amount of study drug in the body at different time points. PD testing measures how the level of study drug in your body may affect the disease. You will need to return to the clinic on the following day (Days 2, 9 and 29 of each cycle \[Day 1 of the next cycle\]) for the last blood draw.

On Day 28 of each cycle:

* You will have a physical exam
* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* You will have an EKG.

Length of Study:

You may receive ibrutinib on this study for up to 3 cycles. After this time, you will continue treatment for CLL as directed by your doctor. This may or may not include ibrutinib. If you do continue to take ibrutinib after the study is over, your doctor will determine the best dose for you to be taking.

You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation in this study will be over after your last dose of ibrutinib (after the end of Cycle 3).

This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of CLL. It is considered investigational to compare 3 different doses of ibrutinib. The study doctor can explain how the study drug is designed to work.

Up to 12 participants will be enrolled in this study. All will take part at MD Anderson.

A Study of Different Doses of Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)

A Pilot Study of Different Doses of Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)

BTK occupancy level measured by fluorescent affinity probe just before dosing and at 4 and 24 hours post-dosing on days 1, 8, and 28 (but before the first dose of the next cycle) of each cycle.

Participants take Ibrutinib capsules by mouth every day for 3, 28 day cycles.

During Cycle 1, participants receive the highest dose of Ibrutinib by taking 3 capsules each day. During Cycle 2, participants receive the second-highest dose and will take 2 capsules each day. During Cycle 3, participant takes the lowest dose of Ibrutinib and takes 1 capsule each day.

Ibrutinib: Cycle 1 daily dose of ibrutinib is 420 mg (3 capsules), in the second cycle 280 mg (2 capsules), and in the third cycle 140 mg (1 capsule).

Age, Continuous

Race (NIH/OMB)

Prithviraj Bose, MD./Associate Professor

Participants With >/= 95 % Bruton's Tyrosine Kinase (BTK) Occupancy

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Hodgkin Disease

Lymphoma, Large-Cell, Anaplastic

Lymphoma, Non-Hodgkin

Peripheral T-cell Lymphoma

Hodgkin Lymphoma

Anaplastic Large Cell Lymphoma

Brentuximab Vedotin

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

Participants receive Brentuximab Vedotin by vein on Day 1 of each cycle.

Participants take TAK228 by mouth either every day, or on a 5 days on/2 days off schedule. The study doctor will tell participant how often to take the study drug.

Each cycle is 21 days.

Participant monitors glucose (sugar) levels at home with a glucose monitor during the first 2 months participant is taking the study drug.

1.8 mg/kg by vein on Day 1 per cycle by vein over about 30 minutes on Day 1 of each cycle.

Starting Dose and Schedule of TAK228: 2 mg by mouth, 5 days on and 2 days off per week with repeated weekly cycles. The study doctor will tell participant how often to take the study drug.

TAK228

Participant monitors glucose (sugar) levels at home with a glucose monitor during the first 2 months participant is taking the study drug.

Glucose Monitor

Michelle A. Fanale, MD

The goal of this clinical research study is to find the highest tolerable dose of TAK228 that can be given in combination with brentuximab vedotin in patients with lymphoma. The safety of this combination will also be studied.

This is an investigational study. TAK228 is not FDA approved or commercially available. It is currently being used for research purposes only. Brentuximab vedotin is FDA approved and commercially available for the treatment of different types of lymphoma. The study doctor can explain how the study drugs are designed to work.

Up to 18 participants will be enrolled in this study. All will take part at MD Anderson.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of TAK228 based on when you join this study. Up to 4 dose levels of TAK228 will be tested. About 3-6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of TAK228 is found.

Your dose of brentuximab vedotin will stay the same. However, if the doctor thinks it is needed for your safety, it may be lowered.

Study Drug Administration:

Each cycle is 21 days.

You will receive brentuximab vedotin by vein over about 30 minutes on Day 1 of each cycle.

You will take TAK228 by mouth either every day or on a 5 days on/2 days off schedule (a "5/2 schedule," where you take the study drug every day for 5 days in a row and then do not take any TAK228 for 2 days in a row). The study doctor will tell you how often to take the study drug.

Each dose of TAK228 should be taken at about the same time each day on an empty stomach with 8 ounces (about 1 cup) of water. You should fast for 2 hours before and 1 hour after each dose.

Length of Study:

You may receive up to 16 cycles of study drugs. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation in this study will be over after about 2 years of follow-up (described below).

Study Visits:

One (1) time every week while receiving the study drugs, blood (about 1-2 tablespoons) will be drawn for routine tests.

Within 3 days before the start of Cycles 2 and beyond:

* You will have a physical exam.
* Blood (about 1-2 tablespoons) will be drawn for routine tests and to check your blood sugar levels. If you can become pregnant, part of this blood sample will be used for a pregnancy test. You should fast for about 8-10 hours before this draw.
* Urine will be collected for routine tests.
* You will have an EKG.

At the end of Cycle 1:

°Blood (about 1-2 tablespoons) will be drawn for biomarker testing.

At the end of Cycle 3 and every 3 cycles after that (Cycles 6, 9, 12, and so on), you will have a CT or PET/CT scan.

At-Home Glucose Monitoring:

You are required to monitor your glucose (sugar) levels at home during the first 2 months you are taking the study drug. If the doctor thinks it is needed, you may be asked to continue monitoring your glucose (sugar) levels at home. The study staff will give you a glucose monitor (called a glucometer) and teach you how and when to use it. You will bring the glucometer with you to each study visit so the study staff can collect the results of the testing.

The study team will tell you what an "abnormal" level is and when to contact the study doctor/study staff.

You will need to return the glucometer to the study staff at the end of the study.

End-of-Dosing Visit:

Within 21 days after your last dose of study drugs:

* You will have a physical exam.
* Blood (about 1-2 tablespoons) will be drawn for routine tests and to check your blood sugar levels. If you can become pregnant, part of this sample will be used for a pregnancy test. You should fast for about 8-10 hours before this draw.
* Urine will be collected for routine tests.
* You will have an EKG.
* You will have a PET/CT or CT scan.

Follow-Up:

Every 4 months for up to 2 years:

* You will have a physical exam.
* Blood (about 1-2 tablespoons) will be drawn for routine tests and to check your blood sugar levels. You should fast for about 8-10 hours before this blood draw.
* You will have a CT scan.

If you are found to be eligible to receive a transplant as part of your standard care, you may receive a transplant. You will sign a separate consent explaining that procedure and its risks in more detail. If you have a stem cell transplant, you will stop having follow-up visits as part of this study.

Study of Brentuximab Vedotin Plus TAK228 for Relapsed/Refractory Classical Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma and Other CD30+Peripheral T-Cell Lymphomas

An Open Label Phase I Study of Brentuximab Vedotin Plus TAK228 for Patients With Relapsed/Refractory Classical Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma and Other CD30+Peripheral T-Cell Lymphomas

DLT defined as a drug-related adverse event during the first cycle of treatment

MTD is the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.

Response determined according to the Lugano Classification.(Cheson, et al 2014)

Takeda

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Nivolumab

Lenalidomide

Ipilimumab

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

The first 4 study cycles are 21 days long, and all remaining cycles are 28 days long.

On Day 1 of Cycles 1-4, Nivolumab by vein over 60 minutes. Thirty (30)minutes after Nivolumab, Ipilimumab given by vein over 90 minutes. On Days 1 and 15 of Cycles 5 and beyond, Nivolumab given by vein over 60 minutes.

Lenalidomide tablets take by mouth on Days 1-14 of Cycles 1-4 and on Days 1-21 of Cycles 5 and beyond. Dexamethasone tablets taken by mouth on Days 1, 8, and 15 of Cycles 1-4, and on Days 1, 8, 15, and 22 of Cycles 5 and beyond.

For participants who are eligible for autologous stem cell transplant, those who achieve at least a partial response after at least 4 cycles of initial therapy will be eligible for:

EITHER Stem cell collection and storage OR Stem cell collection and autologous stem cell transplantation.

Dose Escalation Phase Starting Dose: Nivolumab 1 mg/kg by vein over 60 minutes every 3 weeks for 4 doses, followed by Nivolumab 240 mg by vein every 2 weeks until disease progression or unacceptable toxicity on Days 1 and 15 each cycle.

Dose Expansion Phase Starting Dose: Maximum tolerated dose (MTD) from Dose Escalation Phase.

Maintenance: Nivolumab 240 mg by vein every 2 weeks until disease progression or unacceptable toxicity on Days 1 and 15 each cycle.

Dose Escalation and Dose Expansion Dose: Lenalidomide 25 mg by mouth on Days 1- 14 in 21 day cycles and Days 1-21 in 28 day cycles.

Maintenance: Lenalidomide 10 mg by mouth on Days 1-21.

Dose Escalation and Dose Expansion Dose: Dexamethasone 40 mg by mouth on Days 1,8,15 in 21 day cycles and 1,8,15 and 22 in 28 day cycles

Dose Escalation and Dose Expansion Dose: Ipilimumab 1 mg/kg by vein over 90 minutes every 3 weeks for 4 doses.

Maintenance: If there is evidence of disease progression, Ipilimumab reintroduced at 3 mg/kg every 3 weeks for 4 doses. (Nivolumab dose in Combination determined by the phase 1 portion).

Elisabet E. Manasanch, MD

This study has 2 parts: a Dose Escalation Part and a Dose Expansion Part.

The goal of the Dose Escalation Part of this clinical research study is to find the highest tolerable dose of nivolumab in combination with ipilimumab and the standard of care (lenalidomide and dexamethasone) that can be given to patients with multiple myeloma (MM).

The goal of the Dose Expansion Part of this clinical research study is to continue to study the safety of the highest tolerable dose found in Phase 1 of the study.

Study Groups:

If participant is found to be eligible to take part in this study, participant will be assigned to a study group based on when participant joins this study. Up to 2 groups of up to 6 participants each will be enrolled in the Dose Escalation Part of the study, and up to 24 participants will be enrolled in the Dose Expansion Part.

If participant is enrolled in the Dose Escalation Part, the dose of nivolumab participant receives will depend on when participant joins this study. The first group of participants will receive the lowest dose level of nivolumab. A second group will then receive a higher dose of nivolumab than the group before it, if no intolerable side effects were seen.

If participant is enrolled in the Dose Expansion Part, participant will receive nivolumab at the highest dose that was tolerated in the Dose Escalation Part.

All participants will receive the same dose levels of ipilimumab, dexamethasone, and lenalidomide.

Study Drug Administration:

The first 4 study cycles will be 21 days long, and all remaining cycles will be 28 days long.

On Day 1 of Cycles 1-4, participant will receive nivolumab by vein over 60 minutes. Thirty (30) minutes after participant receives nivolumab, participant will receive ipilimumab by vein over 90 minutes. On Days 1 and 15 of Cycles 5 and beyond, participant will receive nivolumab by vein over 60 minutes.

Participant will take tablets of lenalidomide on Days 1-14 of Cycles 1-4 and on Days 1-21 of Cycles 5 and beyond. Participant will take tablets of dexamethasone on Days 1, 8, and 15 of Cycles 1-4, and on Days 1, 8, 15, and 22 of Cycles 5 and beyond.

Study Visits:

On Day 1 of Cycles 1- 4 (+/- 7 days):

* Participant will have a physical exam.
* Blood (about 3 tablespoons) will be drawn for routine tests, biomarker testing, and to check the status of the disease. If participant can become pregnant, this routine testing will also include a pregnancy test.
* Urine will be collected over 24 hours for routine tests and to check the status of the disease.
* During Cycle 3 only, participant will have 2 bone marrow biopsies/aspirations to check the status of the disease and for biomarker testing, including genetic biomarkers.
* During Cycle 3 only, urine will be collected for biomarker testing.

At the end of Cycle 4, participant will have an ECHO and pulmonary function test to check the status of participant's lungs and heart.

On Day 1 of Cycles 5 and beyond:

* Participant will have a physical exam.
* Blood (about 2 tablespoons) and urine will be collected for routine tests and to check the status of the disease. If participant can become pregnant, this routine testing will also include a pregnancy test.
* Urine will be collected over 24 hours for routine tests and to check the status of the disease.
* Some participants will have a stem cell transplant after Cycle 4. If participant does not have a stem cell transplant, blood (about 1 tablespoon) will be drawn for tests of the immune system every cycle. If participant does have a stem cell transplant, this will only be done every 3 cycles.
* If participant does not have a stem cell transplant, on Day 1 of Cycles 5 and every 3 cycles after that, urine will be collected for biomarker testing.

On Day 15 of Cycles 5 and beyond, blood (about 1 tablespoon) will be drawn for routine tests.

If at any point participant does have a stem cell transplant, participant will have 2 bone marrow biopsies or aspirations to check the status of the disease and for biomarker testing after the transplant.

End-of-Treatment Visits:

When participant stops taking the study drug:

* Blood (about 1-2 tablespoons) and urine will be collected for routine tests, to check the status of the disease, and to learn how the study drugs work in participant's body. If participant can become pregnant, part of this blood will be used for a pregnancy test.
* Participant will have 2 bone marrow biopsies/aspirations to check the status of the disease and for biomarker testing, including genetic biomarkers.

If at any point the disease gets worse:

* Blood (about 2 tablespoons) and urine will be collected for routine tests and to check the status of the disease.
* Urine will be collected over 24 hours for routine tests and to check the status of the disease.
* Participant will have a bone survey to check the status of the disease.
* Participant will have a bone marrow biopsy or aspiration to check the status of the disease and for biomarker testing, including genetic biomarkers.
* Blood (about 3 teaspoons) will be drawn for genetic testing to learn if there is a relationship between participant's genes and the disease

Follow-Up:

If the doctor thinks it is needed, participant may have the following tests. The schedule for these tests will depend on what participant's doctor thinks is in participant's best interest.

* Blood (about 2 tablespoons) and urine will be collected for routine tests and to check the status of the disease. If participant can become pregnant, this routine testing will also include a pregnancy test.
* Urine will be collected over 24 hours for routine tests and to check the status of the disease.
* Participant will have bone marrow biopsies or aspirations to check the status of the disease and for biomarker testing, including genetic biomarkers.
* Participant will have a bone survey to check the status of the disease.

This is an investigational study. Nivolumab and ipilimumab are FDA approved for the treatment of certain types of melanoma. Their use in patients with MM is investigational. Lenalidomide in combination with dexamethasone is FDA approved for the treatment for multiple myeloma. The study doctor can explain how the study drugs are designed to work.

Up to 36 participants will be enrolled in this study. All will take part at MD Anderson.

Study of Lenalidomide/Dexamethasone With Nivolumab and Ipilimumab in Patients With Newly Diagnosed Multiple Myeloma

Phase 1 Study of Lenalidomide/Dexamethasone With Nivolumab and Ipilimumab in Patients With Newly Diagnosed Multiple Myeloma

MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT).

Revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 utilized for AE reporting.

Rate of response determined according to the International Myeloma Working Group Criteria (IMWGC).

PFS defined as time of start of treatment to time of progression to multiple myeloma or death, whichever occurs first.

Overall survival defined as the time of start of treatment to death from any cause.

Duration of overall response is measured from the time measurement criteria are met for initial response until the first date that recurrent or progressive disease is objectively documented.

Clinical benefit rate (CBR) determined assessed by the International Myeloma Working Group Response Criteria).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Blinatumomab Maintenance Following Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Lymphoblastic Leukemia	NCT02807883	Acute Lymphobla...	Blinatumomab Hematopoietic C...	1 Year - 70 Years	M.D. Anderson Cancer Center
Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory B-cell or T-cell Precursor Acute Lymphoblastic Leukemia (ALL)	NCT03207542	Malignant Neopl...	Daratumumab	18 Years -	M.D. Anderson Cancer Center
A Study of Different Doses of Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)	NCT02801578	Chronic Lymphoc...	Ibrutinib	18 Years -	M.D. Anderson Cancer Center
Study of Brentuximab Vedotin Plus TAK228 for Relapsed/Refractory Classical Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma and Other CD30+Peripheral T-Cell Lymphomas	NCT03205891	Malignant Neopl... Classical Hodgk... Anaplastic Larg... CD30+ Periphera...	Brentuximab Ved... TAK228 Glucose Monitor	18 Years -	M.D. Anderson Cancer Center
Study of Lenalidomide/Dexamethasone With Nivolumab and Ipilimumab in Patients With Newly Diagnosed Multiple Myeloma	NCT03283046	Malignant Neopl... Multiple Myelom...	Nivolumab Lenalidomide Dexamethasone Ipilimumab	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for malignant neoplasms stated as primary lymphoid haematopoietic