Graft vs Host Disease
Conditions
Keywords
GVHD
Brief summary
The purpose of this study is to determine the maximum tolerated dose (MTD) of Pregnyl® when given in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk (Arm 1) or refractory/dependent (Arm 2) aGVHD.
Interventions
DRUGPregnyl®
Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 76 Years
Healthy volunteers
No
Inclusion criteria
* Acute graft versus host disease (GVHD) fitting one of the following categories: * High-Risk aGVHD (ARM 1): Pediatric or adult (ages 12-76 years) HCT recipients with high-risk acute GVHD, as determined by the refined MN acute GVHD risk score: http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann Arbor Score 3 or amphiregulin ≥ 33 pg/ml) or * Steroid-Refractory aGVHD (ARM 2): Pediatric or adult (ages 12-76 years) HCT recipient with grade II-IV steroid refractory or steroid-dependent acute GVHD, defined as any one of the following: * No response of acute GVHD after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent * Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent * Failure to improve to at least grade II acute GVHD after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent * Flare of acute GVHD of at least grade II/IV severity despite tapering dose of steroids being \> 0.5 mg/kg/day. * Adequate organ function at study enrollment defined as: * Renal: 1.73m2Serum creatinine ≤2.5x upper limit of normal (ULN) * Cardiac: Left ventricular ejection fraction (LVEF) ≥ 35% * Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)
Exclusion criteria
* Progressive malignancy * Diagnosis of a hormone responsive malignancy * Uncontrolled infection at initiation of protocol treatment * Current thromboembolic disease requiring full-dose anticoagulation - patients receiving pharmacologic prophylaxis for thromboembolic disease will be eligible * Active or recent (within prior 3 months) thrombus, irrespective of anticoagulation status * Pregnancy as assessed on baseline blood hCG level * Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations) * Women or men of childbearing potential unwilling to take adequate precautions to avoid pregnancy from the start of protocol treatment through 28 days after the last treatment Screening Inclusion Criteria: * Pediatric or adult (ages 0-76 years) HCT recipients * Suspected high risk GVHD * Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With No Response | Day 28 after initiation of protocol therapy | Percentage of no response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. No response is defined as deterioration of any organ involved. |
| Phase I: MTD (pg EGF/m^2) | Day 14 after initiation of protocol therapy | Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/m\^2). |
| Number of Patients With Complete Response | Day 28 after initiation of protocol therapy | Percentage of complete response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Complete response is defined as a Stage of 0 for all organs with no additional intervening therapy for their GVHD. |
| Number of Patients With Partial Response | Day 28 after initiation of protocol therapy | Percentage of partial response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Partial response is defined as improvement by at least 1 stage in all involved organs without progression in others with no additional intervening therapy for their GVHD. |
| Number of Patients With Mixed Response | Day 28 after initiation of protocol therapy | Percentage of mixed response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Mixed Response is defined as improvement in one organ with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ. |
| Phase I: MTD (USP hCG) | Day 14 after initiation of protocol therapy | Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/mm\^2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incidence of aGVHD Flare | Day 28 after initiation of protocol therapy | Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 28. |
| Rate of Participants Who Fail Treatment at Day 28 | Day 28 after initiation of protocol therapy | Rate of treatment failure for acute GVHD at day 28 after initiation of protocol therapy to historical controls. |
| Rate of Participants Who Fail Treatment at Day 56 | Day 56 after initiation of protocol therapy | Rate of treatment failure for acute GVHD at day 56 after initiation of protocol therapy to historical controls. |
| Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | Day 70 after initiation of protocol therapy | Safety and feasibility of hCG supplementation with Pregnyl® in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory aGVHD. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 2 |
| Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 2 |
| Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 9 |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 13 |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 4 |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 8 |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 2 |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 5 |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 1 |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 2 |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT).
Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment.
Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7
Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD).
Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m
Phase II: the dose of Pregnyl will be that identified as the MTD during phase I. | 3 |
| Total | 53 |
Baseline characteristics
| Characteristic | Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Total | Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m | Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 | Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 | Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 46 Years | 61 Years | 50 Years | 61 Years | 64 Years | 64 Years | 63 Years | 56.5 Years | 61.5 Years | 61.5 Years | 57 Years | 60.5 Years | 60.5 Years | 64 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 50 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 2 Participants | 7 Participants | 4 Participants | 1 Participants | 13 Participants | 9 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 46 Participants | 3 Participants | 2 Participants | 0 Participants | 5 Participants | 1 Participants | 2 Participants | 7 Participants | 3 Participants | 1 Participants | 12 Participants | 8 Participants | 1 Participants |
| Region of Enrollment United States | 2 participants | 53 participants | 3 participants | 2 participants | 1 participants | 5 participants | 1 participants | 2 participants | 8 participants | 4 participants | 1 participants | 13 participants | 9 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 14 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 39 Participants | 3 Participants | 2 Participants | 0 Participants | 4 Participants | 1 Participants | 1 Participants | 5 Participants | 3 Participants | 1 Participants | 10 Participants | 6 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 1 / 2 | 0 / 9 | 0 / 13 | 0 / 1 | 1 / 4 | 0 / 8 | 0 / 2 | 1 / 1 | 0 / 5 | 1 / 1 | 1 / 2 | 1 / 3 |
| other Total, other adverse events | 1 / 2 | 1 / 2 | 3 / 9 | 6 / 13 | 1 / 1 | 2 / 4 | 5 / 8 | 2 / 2 | 1 / 1 | 3 / 5 | 1 / 1 | 2 / 2 | 1 / 3 |
| serious Total, serious adverse events | 1 / 2 | 1 / 2 | 1 / 9 | 2 / 13 | 1 / 1 | 2 / 4 | 4 / 8 | 2 / 2 | 1 / 1 | 5 / 5 | 0 / 1 | 2 / 2 | 3 / 3 |
Outcome results
Primary
Number of Patients With Complete Response
Percentage of complete response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Complete response is defined as a Stage of 0 for all organs with no additional intervening therapy for their GVHD.
Time frame: Day 28 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Number of Patients With Complete Response | 2 participants |
| 2a: Steroid-Dependent aGVHD | Number of Patients With Complete Response | 2 participants |
| 2b: Steroid-Refractory aGVHD | Number of Patients With Complete Response | 4 participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Complete Response | 7 participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Patients With Complete Response | 1 participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Complete Response | 3 participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Complete Response | 5 participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Number of Patients With Complete Response | 1 participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Patients With Complete Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Complete Response | 2 participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Complete Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Number of Patients With Complete Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Number of Patients With Complete Response | 1 participants |
Primary
Number of Patients With Mixed Response
Percentage of mixed response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Mixed Response is defined as improvement in one organ with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ.
Time frame: Day 28 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Number of Patients With Mixed Response | 0 participants |
| 2a: Steroid-Dependent aGVHD | Number of Patients With Mixed Response | 0 participants |
| 2b: Steroid-Refractory aGVHD | Number of Patients With Mixed Response | 1 participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Mixed Response | 2 participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Patients With Mixed Response | 0 participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Mixed Response | 0 participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Mixed Response | 2 participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Number of Patients With Mixed Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Patients With Mixed Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Mixed Response | 1 participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Mixed Response | 1 participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Number of Patients With Mixed Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Number of Patients With Mixed Response | 0 participants |
Primary
Number of Patients With No Response
Percentage of no response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. No response is defined as deterioration of any organ involved.
Time frame: Day 28 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Number of Patients With No Response | 0 participants |
| 2a: Steroid-Dependent aGVHD | Number of Patients With No Response | 0 participants |
| 2b: Steroid-Refractory aGVHD | Number of Patients With No Response | 4 participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With No Response | 3 participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Patients With No Response | 0 participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With No Response | 1 participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With No Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Number of Patients With No Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Patients With No Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With No Response | 1 participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With No Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Number of Patients With No Response | 1 participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Number of Patients With No Response | 1 participants |
Primary
Number of Patients With Partial Response
Percentage of partial response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Partial response is defined as improvement by at least 1 stage in all involved organs without progression in others with no additional intervening therapy for their GVHD.
Time frame: Day 28 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Number of Patients With Partial Response | 0 participants |
| 2a: Steroid-Dependent aGVHD | Number of Patients With Partial Response | 0 participants |
| 2b: Steroid-Refractory aGVHD | Number of Patients With Partial Response | 0 participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Partial Response | 1 participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Patients With Partial Response | 0 participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Partial Response | 0 participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Partial Response | 1 participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Number of Patients With Partial Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Patients With Partial Response | 1 participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Partial Response | 1 participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Patients With Partial Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Number of Patients With Partial Response | 0 participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Number of Patients With Partial Response | 1 participants |
Primary
Phase I: MTD (pg EGF/m^2)
Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/m\^2).
Time frame: Day 14 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Phase I: MTD (pg EGF/m^2) | 14000 Pregnyl dosage (pg EGF/m^2) |
| 2a: Steroid-Dependent aGVHD | Phase I: MTD (pg EGF/m^2) | 14000 Pregnyl dosage (pg EGF/m^2) |
| 2b: Steroid-Refractory aGVHD | Phase I: MTD (pg EGF/m^2) | 34000 Pregnyl dosage (pg EGF/m^2) |
Primary
Phase I: MTD (USP hCG)
Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/mm\^2).
Time frame: Day 14 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Phase I: MTD (USP hCG) | 2000 Pregnyl dosage (USP hCG) |
| 2a: Steroid-Dependent aGVHD | Phase I: MTD (USP hCG) | 2000 Pregnyl dosage (USP hCG) |
| 2b: Steroid-Refractory aGVHD | Phase I: MTD (USP hCG) | 5000 Pregnyl dosage (USP hCG) |
Secondary
Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl®
Safety and feasibility of hCG supplementation with Pregnyl® in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory aGVHD.
Time frame: Day 70 after initiation of protocol therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1: High-Risk aGVHD | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 1 Participants |
| 2a: Steroid-Dependent aGVHD | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 1 Participants |
| 2b: Steroid-Refractory aGVHD | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 3 Participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 6 Participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 1 Participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 2 Participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 5 Participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 2 Participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 1 Participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 3 Participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 1 Participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 2 Participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl® | 1 Participants |
Secondary
Number of Participants With Incidence of aGVHD Flare
Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 28.
Time frame: Day 28 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| 2a: Steroid-Dependent aGVHD | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| 2b: Steroid-Refractory aGVHD | Number of Participants With Incidence of aGVHD Flare | 3 participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 5 participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 1 participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 1 participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 1 participants |
Secondary
Number of Participants With Incidence of aGVHD Flare
Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 56.
Time frame: Day 56 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| 2a: Steroid-Dependent aGVHD | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| 2b: Steroid-Refractory aGVHD | Number of Participants With Incidence of aGVHD Flare | 2 participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 8 participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 1 participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 4 participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 0 participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 1 participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Number of Participants With Incidence of aGVHD Flare | 1 participants |
Secondary
Rate of Participants Who Fail Treatment at Day 28
Rate of treatment failure for acute GVHD at day 28 after initiation of protocol therapy to historical controls.
Time frame: Day 28 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Rate of Participants Who Fail Treatment at Day 28 | 0 participants |
| 2a: Steroid-Dependent aGVHD | Rate of Participants Who Fail Treatment at Day 28 | 0 participants |
| 2b: Steroid-Refractory aGVHD | Rate of Participants Who Fail Treatment at Day 28 | 8 participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 0 participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 0 participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 1 participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 0 participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 1 participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 0 participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 3 participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 0 participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 1 participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 28 | 1 participants |
Secondary
Rate of Participants Who Fail Treatment at Day 56
Rate of treatment failure for acute GVHD at day 56 after initiation of protocol therapy to historical controls.
Time frame: Day 56 after initiation of protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: High-Risk aGVHD | Rate of Participants Who Fail Treatment at Day 56 | 0 participants |
| 2a: Steroid-Dependent aGVHD | Rate of Participants Who Fail Treatment at Day 56 | 0 participants |
| 2b: Steroid-Refractory aGVHD | Rate of Participants Who Fail Treatment at Day 56 | 2 participants |
| Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 9 participants |
| Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 0 participants |
| Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 2 participants |
| Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 4 participants |
| Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 1 participants |
| Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 0 participants |
| Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 2 participants |
| Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 1 participants |
| Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 1 participants |
| Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 | Rate of Participants Who Fail Treatment at Day 56 | 1 participants |