Nivolumab and Tocilizumab for Relapsed Hematological Malignancy Post-allogeneic Transplant

NCT03588936 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PRO32525
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, interventional single arm, open label, treatment study designed to evaluate the safety combination programmed cell death protein 1 (PD-1) and interleukin 6 (IL-6) inhibition in participants with relapsed disease post-allogeneic transplant.

Conditions

Acute Leukemia; Chronic Leukemia; Lymphoma; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated Dose

  Determine the safety and the maximum tolerated dose among two candidate doses of nivolumab in combination with tocilizumab for treatment of relapsed hematological malignancy post-allogeneic transplant. Maximum-tolerated dose is based on the determination of dose-limiting toxicities.

  Up to 4 weeks after last dose of study treatment (approximately 3 months)

Secondary Outcomes (6)

• Response Rates Based on Imaging

  End of study treatment (approximately 2 months)

• Response Rates Based on Pathologic Response

  End of study treatment (approximately 2 months)

• Overall Survival

  Up to 1 year from beginning of treatment

• Progression-Free Survival

  Up to 1 year from beginning of treatment

• Duration of response in responding participants

  Up to 1 year from the beginning of treatment

Study Arms (2)

Nivolumab (0.25 mg/kg) and Tocilizumab

EXPERIMENTAL

Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.25 mg/kg based on dose escalation design). Nivolumab will be given every \~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on \~Day 29 on the same day as Dose # 3 of Nivolumab.

Drug: Nivolumab (.25 mg/kg); Drug: Tocilizumab

Nivolumab (0.5 mg/kg) and Tocilizumab

EXPERIMENTAL

Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.5 mg/kg based on dose escalation design). Nivolumab will be given every \~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on \~Day 29 on the same day as Dose # 3 of Nivolumab.

Drug: Tocilizumab; Drug: Nivolumab (.5 mg/kg)

Interventions

Nivolumab (.25 mg/kg) DRUG

Participants will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments.

Also known as: OPDIVO

Nivolumab (0.25 mg/kg) and Tocilizumab

Tocilizumab DRUG

Participants will receive 2 doses of tocilizumab

Also known as: ACTEMRA

Nivolumab (0.25 mg/kg) and Tocilizumab; Nivolumab (0.5 mg/kg) and Tocilizumab

Nivolumab (.5 mg/kg) DRUG

Participants will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments.

Also known as: OPDIVO

Nivolumab (0.5 mg/kg) and Tocilizumab

Eligibility Criteria

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

You may qualify if:

• Age≥18 years with hematological malignancies who have undergone allogeneic transplant for hematological malignancy and are ≥180 days post-transplant.
• Relapsed disease post-allogeneic transplant defined as follows i. Acute or Chronic Leukemia or myelodysplastic or myeloproliferative disorders or natural killer (NK) cell neoplasms: Bone marrow (BM) with ≥5% disease involvement or peripheral blood evidence of overt relapse ii. Lymphoma: BM evidence of relapsed/persistent disease or PET/CT or CT evidence of persistent/progressive lymphadenopathy consistent with active lymphoma. Active disease defined as nodal lesions ≥ 20 mm in the long axis or extranodal lesions≥10 mm in long and short axis or bone marrow involvement that is biopsy proven
• Karnofsky performance status ≥70 (See Appendix A for details)
• Creatinine Clearance≥60 ml/min
• Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN). Serum bilirubin and alkaline phosphatase ≤3x x ULN, or considered not clinically significant (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease.
• Without evidence of active acute or chronic graft versus host disease (GVHD)
• Off all immunosuppression and corticosteroids (other than replacement dose steroids defined as equivalent to a maximum of 10 mg Prednisone daily) for ≥28 days from first treatment.
• Off all disease targeted treatments for ≥10 days to first treatment day
• Able to provide written informed consent
• Women of child-bearing potential and men must agree to use adequate contraception for the duration of study participation and for 120 days after the last treatment with nivolumab.
• No FDA approved, more appropriate therapies available for disease control as determined by the treating physician

You may not qualify if:

• Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential
• Cluster of differentiation 3 (CD3) donor chimerism \<5% within 4 weeks of starting study treatment
• Prior administration of donor lymphocyte infusion post-allogeneic transplant within the last 6 months of study treatment
• History of or active autoimmune disease, or other syndrome that requires systemic steroids.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
• Uncontrolled or active infections on treatment
• Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.
• Presence of ≥grade 3 non-hematologic toxicities as per CTCAE version 5 from any previous treatment unless it is felt to be due to underlying disease.
• Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution.
• a. Minimum of 4 weeks from last dose of investigational agent
• Prior exposure to PD-1 or CTLA4 antibodies in the post-allogeneic transplant setting. Participants who received such agents pre-allogeneic transplant will NOT be excluded.
• Prior exposure to daratumumab in the post-allogeneic transplant setting within two months of start date of treatment with this investigational protocol. Participants who received this agent pre-allogeneic transplant will NOT be excluded
• Concurrent therapies targeted at disease relapse. However, previous treatments for relapsed disease are allowed.
• Concurrent active malignancy (exceptions: treated solid malignancy in \>2 years' remission, treated basal or squamous cell carcinomas of the skin)
• History of Crohn's disease or ulcerative colitis

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Lymphoma; Myelodysplastic Syndromes

Interventions

Nivolumab; tocilizumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nirav Shah, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 4, 2018
• First Posted: July 17, 2018
• Study Start: September 14, 2018
• Primary Completion: July 15, 2020
• Study Completion: July 15, 2020
• Last Updated: October 11, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)