GVHD Prophylaxis With Post Transplant Cyclophosphamide for Patients With Renal Insufficiency Undergoing a Conventional 8/8 HLA-matched Related or Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplant

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02360111
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arm: 1
• Actual Duration (Months): 31
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a pilot study which will be done in a small number of patients. The purpose of this study is to test the safety and benefit of giving a type of chemotherapy - cyclophosphamide - after the transplant to prevent graft versus host disease (GVHD) in patients with abnormal kidney function. GVHD is one of the most common complications of a stem cell transplant .

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma	Drug: Cyclophosphamide	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Trial of GVHD Prophylaxis With Post Transplant Cyclophosphamide for Patients With Renal Insufficiency Undergoing a Conventional 8/8 HLA-matched Related or Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplant
• Actual Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Post Transplant Cyclophosphamide Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7.	Drug: Cyclophosphamide

Outcome Measures

Primary Outcome Measures

1. # GVHD (Grade II-IV) Chronic GVHD Will be Diagnosed and Graded According to the (NIH Criteria) [2 years]

   Chronic GVHD will be diagnosed and graded according to the (NIH criteria) treated with standard or experimental immunosuppressive therapy.

Secondary Outcome Measures

1. Disease-free Survival [2 years]

   DFS is defined as the minimum interval of time to relapse/recurrence, to death or to the last follow-up, from the time of transplant

2. Overall Survival [2 years]

   Overall survival is defined as time from transplant to death or last follow-up.

3. # Renal Insufficiency Defined as a Calculated eGFR <60 ml/Min/1.73m2. Those With a eGFR < 30 ml/Min/1.73m2 Will be Considered Ineligible. [2 years]

   Renal insufficiency is defined as a calculated eGFR <60 ml/min/1.73m2. Those with a eGFR < 30 ml/min/1.73m2 will be considered ineligible.

4. The Occurrence of Life-threatening Opportunistic Infections [2 years]

   will be evaluated according to the criteria established by BMT CTN , and will be correlated with the level of immune recovery.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age: Patients over age 18 who are deemed eligible for transplant by their treating physician.

• Disease status:

1. AML in ≥ 1st remission - excluding those in 1st remission with 'good risk' cytogenetic features (i.e. t(8;21), t(15;17), inv 16).

2. Secondary AML

3. ALL/LL in 1st remission with clinical or molecular features indicating a high risk for relapse; or ALL > 2nd remission

4. CML failing to respond to, progressing on or not tolerating appropriate TKI therapy in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR after accelerated phase or blast crisis.

5. Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories:

6. high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants or transplants requiring the use of calcineurin inhibitors.

7. any NHL with therapy responsive disease which is considered not curable outside the transplant setting and not eligible/appropriate for autologous transplant or a higher priority protocol.

8. Myelodysplastic syndrome (MDS): RA/RCMD with high risk cytogenetic features or transfusion dependence, RAEB-1 and RAEB-2 and AML evolved from MDS, who are not eligible for a higher priority protocol.

9. Chronic myelomonocytic leukemia: CMML-1 and CMML-2, advanced polycythemia vera, and myelofibrosis.

10. Patients must have a healthy HLA compatible (8/8 molecularly matched related, or unrelated) donor willing to undergo BM harvesting or PBSC apheresis after G-CSF administration. BM will be the preferred graft source.

11. Patients diagnosed with any form of acute leukemia must have received induction and at least one course of consolidation chemotherapy pretransplant

• Patients must have a Karnofsky Performance Status > 70%

• Patients will have a eGFR <60 ml/min/1.73 m2

1. Patients must have adequate organ function measured by: Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve with exercise.

2. Hepatic: ALT < 3 x ULN and total serum bilirubin < 1.5 x ULN, unless there is congenital benign hyperbilirubinemia

3. Renal: eGFR > 30 ml/min/1.73 m2

4. Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)

• Each patient must be willing to participate as a research subject and must sign an informed consent form.

• Patient must have a fully matched related or unrelated donor willing to donate stem cells.

Exclusion Criteria:

• Major surgery or irradiation within two weeks.

• Active CNS or extramedullary malignant disease.

• Active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold, or HIV infection

• Pregnant or lactating women - they are excluded, given the potential teratogenic effects of chemotherapy and agents used in the transplant.

• Male and female patients of child-bearing potential unwilling to use effective means of contraception

• HIV or HTLV I/II positive, hepatitis C or chronic active hepatitis B.

• Patients who have had a previous malignancy unless they are deemed by their treating physicians to be at low risk for recurrence.

• Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Ann Jakubowski, Ph.D., M.D., Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 25, 2017

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT02360111
• Other Study ID Numbers: 14-273
• First Posted: Feb 10, 2015
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Memorial Sloan Kettering Cancer Center: GVHD Prophylaxis; Cyclophosphamide; Renal Insufficiency; Hematopoietic Stem Cell Transplant; 14-273
• Additional relevant MeSH terms: Renal Insufficiency; Myelodysplastic Syndromes; Cyclophosphamide

Study Results

Participant Flow

Arm/Group Title	Post Transplant Cyclophosphamide
Arm/Group Description	Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7. Cyclophosphamide
Period Title: Overall Study
STARTED	3
COMPLETED	1
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Post Transplant Cyclophosphamide
Arm/Group Description	Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7. Cyclophosphamide
Overall Participants	3
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	3 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	3 100%

Outcome Measures

1. Primary Outcome

Title	# GVHD (Grade II-IV) Chronic GVHD Will be Diagnosed and Graded According to the (NIH Criteria)
Description	Chronic GVHD will be diagnosed and graded according to the (NIH criteria) treated with standard or experimental immunosuppressive therapy.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Protocol terminated prematurely due to low accrual

Arm/Group Title	Post Transplant Cyclophosphamide
Arm/Group Description	Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7. Cyclophosphamide
Measure Participants	0

2. Secondary Outcome

Title	Disease-free Survival
Description	DFS is defined as the minimum interval of time to relapse/recurrence, to death or to the last follow-up, from the time of transplant
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Protocol terminated prematurely due to low accrual

Arm/Group Title	Post Transplant Cyclophosphamide
Arm/Group Description	Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7. Cyclophosphamide
Measure Participants	0

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as time from transplant to death or last follow-up.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Protocol terminated prematurely due to low accrual

Arm/Group Title	Post Transplant Cyclophosphamide
Arm/Group Description	Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7. Cyclophosphamide
Measure Participants	0

4. Secondary Outcome

Title	# Renal Insufficiency Defined as a Calculated eGFR <60 ml/Min/1.73m2. Those With a eGFR < 30 ml/Min/1.73m2 Will be Considered Ineligible.
Description	Renal insufficiency is defined as a calculated eGFR <60 ml/min/1.73m2. Those with a eGFR < 30 ml/min/1.73m2 will be considered ineligible.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Protocol terminated prematurely due to low accrual

Arm/Group Title	Post Transplant Cyclophosphamide
Arm/Group Description	Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7. Cyclophosphamide
Measure Participants	0

5. Secondary Outcome

Title	The Occurrence of Life-threatening Opportunistic Infections
Description	will be evaluated according to the criteria established by BMT CTN , and will be correlated with the level of immune recovery.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Protocol terminated prematurely due to low accrual

Arm/Group Title	Post Transplant Cyclophosphamide
Arm/Group Description	Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7. Cyclophosphamide
Measure Participants	0

Adverse Events

Time Frame	24 months
Arm/Group Title	Post Transplant Cyclophosphamide
Arm/Group Description	Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7. Cyclophosphamide
All Cause Mortality
	Post Transplant Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Serious Adverse Events
	Post Transplant Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Cardiac disorders
Pericardial effusion	1/3 (33.3%)
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)
General disorders
Edema limbs	1/3 (33.3%)
Infections and infestations
Lung infection	2/3 (66.7%)
Salivary gland infection	1/3 (33.3%)
Sepsis	3/3 (100%)
Nervous system disorders
Encephalopathy	1/3 (33.3%)
Psychiatric disorders
Delirium	1/3 (33.3%)
Renal and urinary disorders
Acute kidney injury	1/3 (33.3%)
Urinary retention	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/3 (33.3%)
Respiratory failure	1/3 (33.3%)
Skin and subcutaneous tissue disorders
Purpura	1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	Post Transplant Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Blood and lymphatic system disorders
Anemia	3/3 (100%)
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)
General disorders
Edema limbs	1/3 (33.3%)
Infections and infestations
Lung infection	1/3 (33.3%)
Sepsis	1/3 (33.3%)
Investigations
Lymphocyte count decreased	3/3 (100%)
Neutrophil count decreased	3/3 (100%)
Platelet count decreased	3/3 (100%)
White blood cell decreased	3/3 (100%)
Aspartate aminotransferase increased	1/3 (33.3%)
Blood bilirubin increased	1/3 (33.3%)
Creatinine increased	1/3 (33.3%)
Metabolism and nutrition disorders
Hyperkalemia	2/3 (66.7%)
Hypokalemia	2/3 (66.7%)
Hyperglycemia	1/3 (33.3%)
Hypocalcemia	1/3 (33.3%)
Hyponatremia	1/3 (33.3%)
Hypophosphatemia	1/3 (33.3%)
Nervous system disorders
Encephalopathy	1/3 (33.3%)
Syncope	1/3 (33.3%)
Psychiatric disorders
Delirium	1/3 (33.3%)
Renal and urinary disorders
Acute kidney injury	1/3 (33.3%)
Urinary retention	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/3 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.