NCT00423514

Clofarabine, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk and/or Advanced Hematologic Cancer or Other Disease

Completed Phase 1, PHASE2 Results posted Last updated 27 December 2022

What this trial tests

Phase 1, PHASE2 trial testing filgrastim in Graft Versus Host Disease in 38 participants. Completed in 18 June 2021.

Timeline

20 November 2006

Primary endpoint
18 June 2021

18 June 2021

Quick facts

Lead sponsor	Memorial Sloan Kettering Cancer Center
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	38
Start date	20 November 2006
Primary completion	18 June 2021
Estimated completion	18 June 2021
Sites	1 location across United States

Drugs / interventions tested

• filgrastim
• clofarabine (CLOFARABINE) — full drug profile →
• melphalan
• mycophenolate mofetil (MYCOPHENOLATE MOFETIL) — full drug profile →
• tacrolimus (TACROLIMUS) — full drug profile →
• thiotepa — full drug profile →
• allogeneic bone marrow transplantation
• allogeneic hematopoietic stem cell transplantation — full drug profile →
• peripheral blood stem cell transplantation

Conditions studied

• Graft Versus Host Disease — all drugs for Graft Versus Host Disease →
• Leukemia — all drugs for Leukemia →
• Myelodysplastic Syndromes — all drugs for Myelodysplastic Syndromes →

Sponsor

Memorial Sloan Kettering Cancer Center — full company profile →

Who can join

Adults 0 to 54, any sex, with Graft Versus Host Disease or Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Response to Therapy Primary · 1 year

* A complete response (CR) will be defined as less than 5% bone marrow blasts in the setting of a neutrophil count of \>/= 1.0 K/ul and a platelet count of \>/= 75,000/ul * A complete response except platelets (CRp) will be defined as less than 5% bone marrow blasts in the setting of a neutrophil count of \>/= 1.0 K/ul and a platelet count of \>/= 75,000/ul * A partial response (PR) will be defined as 5%-25% bone marrow blasts in the setting of a neutrophil count of \>/= 1.0 K/ul and a platelet count of \>/= 75,000/ul * A partial response except platelets (PRp) will be defined as 5%-25% bone m

Group	Value	95% CI
Dose Level 1: Clofarabine at 20 mg/m^2/Dose x 5 + THIO-MEL	1
Dose Level 2: Clofarabine at 30 mg/m^2/Dose x 5 + THIO-MEL	0
Dose Level 1: Clofarabine at 20 mg/m^2/Dose x 5 + THIO-MEL	27
Dose Level 2: Clofarabine at 30 mg/m^2/Dose x 5 + THIO-MEL	4
Dose Level 1: Clofarabine at 20 mg/m^2/Dose x 5 + THIO-MEL	3
Dose Level 2: Clofarabine at 30 mg/m^2/Dose x 5 + THIO-MEL	3

Overall Survival Primary · 1 year

Group	Value	95% CI
Dose Level 1: Clofarabine at 20 mg/m^2/Dose x 5 + THIO-MEL	19
Dose Level 2: Clofarabine at 30 mg/m^2/Dose x 5 + THIO-MEL	4
Dose Level 1: Clofarabine at 20 mg/m^2/Dose x 5 + THIO-MEL	12
Dose Level 2: Clofarabine at 30 mg/m^2/Dose x 5 + THIO-MEL	3

Participants Evaluated for Early Post-transplant Regimen-related Severe Morbidity (Grade III to IV Nonhematologic Toxicity) and Mortality as Measured by the NCI Cancer Therapy Evaluation Program CTCAE v 3.0 Secondary · 1 year

Group	Value	95% CI
Dose Level 1: Clofarabine at 20 mg/m^2/Dose x 5 + THIO-MEL	31
Dose Level 2: Clofarabine at 30 mg/m^2/Dose x 5 + THIO-MEL	7

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Level 1: Clofarabine at 20 mg/m^2/Dose x 5 + THIO-MEL

Serious: 8/31 (26%)

Deaths: 12/31

Dose Level 2: Clofarabine at 30 mg/m^2/Dose x 5 + THIO-MEL

Serious: 3/7 (43%)

Deaths: 3/7

Serious adverse events (17 terms)

Reaction	System	Dose Level 1: Clofarabine …	Dose Level 2: Clofarabine …
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Renal failure	Renal and urinary disorders	—	—
CNS cerebrovascular ischemia	Nervous system disorders	—	—
Death not assoc w CTCAE term - Disease prog NOS	General disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Encephalopathy	Nervous system disorders	—	—
Hypertension	Vascular disorders	—	—
Ileus, GI (func obstruction of bowel)	Gastrointestinal disorders	—	—
Infection, other	Infections and infestations	—	—
Liver dysfunction/failure	Hepatobiliary disorders	—	—
Metabolic/Lab - Other (specify)	Metabolism and nutrition disorders	—	—
Mucositis (Clin exam) - Oral cavity	Gastrointestinal disorders	—	—
Pneumonitis/pulm infiltrates	Respiratory, thoracic and mediastinal disorders	—	—
Pulm/upp respiratory - Other (spec)	Respiratory, thoracic and mediastinal disorders	—	—
Rash; erythema multiforme	Skin and subcutaneous tissue disorders	—	—
Secondary malig - poss related to ca txt specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Thrombosis/thrombus/embolism	Vascular disorders	—	—

Other adverse events (19 terms — click to expand)

Reaction	System	Dose Level 1: Clofarabine …	Dose Level 2: Clofarabine …
Hemoglobin	Blood and lymphatic system disorders	—	—
Leukocytes (total WBC)	Investigations	—	—
Lymphopenia	Investigations	—	—
Neutrophils/granulocytes (ANC/AGC)	Investigations	—	—
Platelets	Investigations	—	—
ALT, SGPT	Investigations	—	—
Glucose, high (hyperglycemia)	Metabolism and nutrition disorders	—	—
AST, SGOT	Investigations	—	—
Potassium, low (hypokalemia)	Metabolism and nutrition disorders	—	—
Magnesium, high (hypermagnesemia)	Metabolism and nutrition disorders	—	—
Sodium, low (hyponatremia)	Metabolism and nutrition disorders	—	—
Bilirubin (hyperbilirubinemia)	Investigations	—	—
Phosphate, low (hypophosphatemia)	Metabolism and nutrition disorders	—	—
Potassium, high (hyperkalemia)	Metabolism and nutrition disorders	—	—
PTT	Investigations	—	—
Creatinine	Investigations	—	—
Fibrinogen	Investigations	—	—
Alkaline phosphatase	Investigations	—	—
INR	Investigations	—	—

Most-reported serious reactions: Hypoxia, Renal failure, CNS cerebrovascular ischemia, Death not assoc w CTCAE term - Disease prog NOS, Diarrhea, Encephalopathy, Hypertension, Ileus, GI (func obstruction of bowel).

Data from ClinicalTrials.gov NCT00423514 adverse events section.

Sponsor's own description

RATIONALE: Giving chemotherapy, such as clofarabine, melphalan, and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with melphalan and thiotepa, followed by a donor stem cell transplant and to see how well it works in treating patients with high-risk and/or advanced hematologic cancer or other disease.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts.
   Avery S, Shi W, Lubin M, Gonzales AM, et al · · 2011 · cited 99× · PMID 21149633 · DOI 10.1182/blood-2010-08-300491
2. Second Allogeneic Stem Cell Transplantation for Acute Leukemia Using a Chemotherapy-Only Cytoreduction with Clofarabine, Melphalan, and Thiotepa.
   Spitzer B, Perales MA, Kernan NA, Prockop SE, et al · · 2016 · cited 8× · PMID 27184623 · DOI 10.1016/j.bbmt.2016.05.001