Ipilimumab or Nivolumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplant

NCT01822509 | Completed Phase 1 DMC

• 7 other identifiers: NCI-2013-0073912-5379204P30CA006516R01CA183559U01CA062490UM1CA186709
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 13

Brief Summary

This phase I/Ib trial studies the side effects and best dose of ipilimumab or nivolumab in treating patients with cancers of the blood and blood-forming tissues (hematologic cancers) that have returned after a period of improvement (relapsed) after donor stem cell transplant. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Allogeneic Hematopoietic Stem Cell Transplant Recipient; Myeloproliferative Neoplasm; Recurrent Acute Lymphoblastic Leukemia; Recurrent Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Hematologic Malignancy; Recurrent Hodgkin Lymphoma; Recurrent Myelodysplastic Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) of ipilimumab according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase I)

  Dose-limiting toxic (DLT) effects were defined as grade III or IV acute graft versus host disease (GVHD), grade 4 hematologic toxic effects unrelated to the underlying disease, or grade 3 nonhematologic toxic effects that did not improve to grade 1 with a 3-week dose delay. Immune-related adverse events that resolved to grade 1 or lower with the use of glucocorticoids were not considered to be dose-limiting toxic effects. We designated the observation period for toxic effects to be 12 weeks to capture delayed immunologic toxic effects.

  At 12 weeks

• Maximum tolerated dose (MTD) of nivolumab according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase I)

  Dose-limiting toxic (DLT) effects are defined as grade III or IV acute GVHD, grade 4 hematologic toxic effects unrelated to the underlying disease, or grade 3 nonhematologic toxic effects that did not improve to grade 1 with a 3-week dose delay. Immune-related adverse events that resolved to grade 1 or lower with the use of glucocorticoids were not considered to be dose-limiting toxic effects. We designated the observation period for toxic effects to be 12 weeks to capture delayed immunologic toxic effects.

  At 12 weeks

• Incidence of adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Phase Ib)

  A serious adverse event (SAE) is any adverse event, occurring at any dose and regardless of causality that 1) Results in death, 2) Is life-threatening, 3) Requires or prolongs inpatient hospitalization, 4) Results in persistent or significant disability/incapacity, 5) Is an important medical event when, based upon appropriate medical judgment, it may jeopardize the participant and require medical or surgical intervention to prevent one of the outcomes listed above.

  Up to 1 year after completion of study treatment

Secondary Outcomes (3)

• Clinical response

  Up to 1 year

• Progression-free survival (PFS)

  From start of treatment to time of objective disease progression, assessed up to 1 year

• Overall survival (OS)

  From the start of treatment to time of death, assessed up to 1 year

Other Outcomes (2)

• Change in immune cell numbers

  Baseline to up to 1 year

• Change in cytokine production

  Baseline to up to 1 year

Study Arms (1)

Treatment (ipilimumab, nivolumab)

EXPERIMENTAL

See Detailed Description.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Treatment (ipilimumab, nivolumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ipilimumab, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (ipilimumab, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed hematologic malignancy
• The following malignancies will be considered eligible if progressive or persistent:
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)
• Hodgkin lymphoma (HL)
• Multiple myeloma (MM)
• Acute leukemia (acute myeloid leukemia \[AML\], acute lymphoblastic leukemia \[ALL\])
• Myelodysplastic syndrome (MDS)
• Myeloproliferative neoplasms (MPN)
• Chronic myeloid leukemia (CML)
• Life expectancy of greater than 3 months
• Must have undergone allogeneic hematopoietic stem cell transplantation (HSCT) (regardless of stem cell source)
• Must have baseline donor T cell chimerism of \>= 20%
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (unless due to Gilbert's disease or disease-related hemolysis, then =\< 3.0 x ULN)

You may not qualify if:

• Participants who have had anti-tumor therapy or other investigational agents within 4 weeks prior to registration (6 weeks for nitrosoureas or mitomycin C), or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to registration
• Patients with prior history of or active severe (grade 3 or 4) acute graft-versus-host disease (GVHD)
• Patients with a history of prior treatment with ipilimumab, anti-programmed cell death protein 1 (PD 1) antibody, or cluster of differentiation (CD)137 agonist therapy are ineligible for the ipilimumab arm, but are eligible for the nivolumab arm
• Patients who have had donor lymphocyte infusion (DLI) within 8 weeks prior to registration
• Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]) and motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis); patients with Hashimoto's thyroiditis are eligible to go on study
• Patients with known chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections should be excluded
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because ipilimumab and nivolumab are immunomodulatory agents with the potential for teratogenic or abortifacient effects; the effects of ipilimumab and nivolumab on the developing human fetus are unknown; for this reason and because immunomodulatory agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study or within 23 weeks after the last dose of study drug, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for at least 31 weeks after completion of ipilimumab or nivolumab administration

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (13)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Moffitt Cancer Center-International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Lafayette Family Cancer Center-EMMC

Brewer, Maine, 04412, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Related Publications (3)

• Penter L, Zhang Y, Savell A, Huang T, Cieri N, Thrash EM, Kim-Schulze S, Jhaveri A, Fu J, Ranasinghe S, Li S, Zhang W, Hathaway ES, Nazzaro M, Kim HT, Chen H, Thurin M, Rodig SJ, Severgnini M, Cibulskis C, Gabriel S, Livak KJ, Cutler C, Antin JH, Nikiforow S, Koreth J, Ho VT, Armand P, Ritz J, Streicher H, Neuberg D, Hodi FS, Gnjatic S, Soiffer RJ, Liu XS, Davids MS, Bachireddy P, Wu CJ. Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation. Blood. 2021 Jun 10;137(23):3212-3217. doi: 10.1182/blood.2021010867.

  PMID: 33720354 DERIVED

• Davids MS, Kim HT, Costello C, Herrera AF, Locke FL, Maegawa RO, Savell A, Mazzeo M, Anderson A, Boardman AP, Weber A, Avigan D, Chen YB, Nikiforow S, Ho VT, Cutler C, Alyea EP, Bachireddy P, Wu CJ, Ritz J, Streicher H, Ball ED, Bashey A, Soiffer RJ, Armand P. A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation. Blood. 2020 Jun 11;135(24):2182-2191. doi: 10.1182/blood.2019004710.

  PMID: 32478814 DERIVED

• Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, LeBoeuf NR, Rooney MS, Bowden M, Zhou CW, Granter SR, Hornick JL, Rodig SJ, Hirakawa M, Severgnini M, Hodi FS, Wu CJ, Ho VT, Cutler C, Koreth J, Alyea EP, Antin JH, Armand P, Streicher H, Ball ED, Ritz J, Bashey A, Soiffer RJ; Leukemia and Lymphoma Society Blood Cancer Research Partnership. Ipilimumab for Patients with Relapse after Allogeneic Transplantation. N Engl J Med. 2016 Jul 14;375(2):143-53. doi: 10.1056/NEJMoa1601202.

  PMID: 27410923 DERIVED

MeSH Terms

Conditions

Myeloproliferative Disorders; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Hodgkin Disease; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Multiple Myeloma

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Matthew S Davids

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2013
• First Posted: April 2, 2013
• Study Start: May 16, 2013
• Primary Completion: December 31, 2018
• Study Completion: June 10, 2021
• Last Updated: June 24, 2021

Record last verified: 2021-06

Locations

US (13)